Applications of Substituent Benzyloxy Group Containing Ether Compounds for Preparing Antitumor Drugs

ABSTRACT

Disclosed are applications of substituent benzyloxy group containing ether compounds represented by general formula I for preparing antitumor drugs. 
     
       
         
         
             
             
         
       
     
     The definition of the substituent groups in the formula I are provided in the specification. 
     The compounds having general formula I have desirable antitumor activity, particularly, and have excellent activity against leukemia strain HL-60, lung cancer A549, H157, H460, H520, bladder cancer T24, J82, prostate cancer LNCap, PC-3, rectal cancer HCT8, HCT116, RkO and the like.

FIELD OF THE INVENTION

The present invention belongs to the field of medicine, relating to the field of antitumor drugs. Specifically to applications of substituent benzyloxy group containing ether compounds for preparing antitumor drugs.

BACKGROUND OF THE INVENTION

The following journals and patents disclosed benzopyrone compounds containing methoxyacrylate with fungicidal activity in agrochemical field: Pest Management Science, Volume: 67, Issue: 6, Pages: 647-655; Natural Product Communications, Volume: 6, Issue: 12, Pages: 1917-1920; Nongyao, Volume: 50, Issue: 2, Pages: 90-92; Nongyaoxue Xuebao, Volume: 12, Issue: 4, Pages: 453-457; Natural Product Communications, Volume: 2, Issue: 8, Pages: 845-848; Chinese Chemical Letters, Volume: 22, Issue: 6, Pages: 663-666; WO 2005044813.

Journal of Medicinal Chemistry, Volume: 50, Issue: 12, Pages: 2886-2895 reported the following general formula containing benzopyrone group with antiplatelet activity.

Bioorganic & Medicinal Chemistry Letters 23(2013) 3505-3510 disclosed a strobilurin compound containing substituted pyrimidinamines with some antitumor activity, the structure of compound 96 (compound A in this patent) is as follows:

Patent U.S. Pat. No. 6,084,120 disclosed the compound having following general formula has some inhibition effect on Plasmodium falciparum NF54 strain and plasmodium berghei, however, compound B was reported at the same time without any biological data. Patent U.S. Pat. No. 7,947,734 also disclosed compound B (that is flufenoxystrobin) with good fungicidal and acaricidal activity in agrochmical field.

In the prior art, the substituent benzyloxy group containing ether compounds having the structure of general formula I were not reported as antitumor agents.

SUMMARY OF THE INVENTION

The object of the present invention is to provide substituent benzyloxy group containing ether compounds having general formula I, which can be applied to prepare antitumor drugs.

Detailed Description of the Invention is as Follows:

The application of substituent benzyloxy group containing ether compounds for preparing antitumor drugs, the compounds having the structure of general formula I:

Wherein:

Ar is selected from one of the following groups, Ar1 to Ar16:

Q is selected from one of the following groups, Q1 to Q22:

R₁, R₂, R₃, R₄, R₅, R₆ mutually independently may be the same or different, selected from H, halo, CN, NO₂, OH, NH₂, CHO, CO₂H, CO₂Na, CO₂NH₄, C₁-C₁₂alkyl, C₁-C₁₂haloalkyl, C₃-C₈cycloalkyl, C₁-C₁₂alkoxy, C₁-C₁₂haloalkoxy, C₁-C₁₂alkylthio, C₁-C₁₂haloalkylthio, C₁-C₁₂alkoxyC₁-C₁₂alkyl, haloC₁-C₁₂alkoxyC₁-C₁₂alkyl, C₁-C₁₂alkoxyC₁-C₁₂alkoxy, haloC₁-C₁₂alkoxyC₁-C₁₂alkoxy, C₁-C₁₂alkylthioC₁-C₁₂alkyl, haloC₁-C₁₂alkylthioC₁-C₁₂alkyl, C₁-C₁₂alkylamino, C₁-C₁₂haloalkylamino, C₂-C₁₂dialkylamino, C₂-C₁₂halodialkylamino, piperidinyl, pyrrolidinyl, N-methylpiperidinyl, morpholinyl, C₂-C₁₂alkenyl, C₂-C₁₂haloalkenyl, C₂-C₁₂alkynyl, C₂-C₁₂haloalkynyl, C₂-C₁₂alkenyloxy, C₂-C₁₂haloalkenyloxy, C₂-C₁₂alkynyloxy, C₂-C₁₂haloalkynyloxy, C₁-C₁₂alkylsulfonyl, C₁-C₁₂haloalkylsulfonyl, C₁-C₁₂alkylsulfinyl, C₁-C₁₂haloalkylsulfinyl, C₁-C₁₂alkylcarbonyl, C₁-C₁₂haloalkylcarbonyl, C₁-C₁₂alkylcarbonyloxy

C₁-C₁₂alkylcarbonylamino, C₁-C₁₂alkylsulfonyloxy, C₁-C₁₂alkoxycarbonyl, C₁-C₁₂haloalkoxycarbonyl, C₁-C₁₂alkylaminosulfonyl, C₁-C₁₂alkoxycarbonylamino, C₁-C₁₂alkoxycarbonylC₁-C₁₂alkyl, C₁-C₁₂alkoxycarbonylC₁-C₁₂alkoxy, aminoC₁-C₁₂alkyl, C₁-C₁₂alkylaminoC₁-C₁₂alkyl, C₂-C₁₂dialkylaminoC₁-C₁₂alkyl, C(═O)NR₁₀R₁₁, OC(═O)NR₁₀R₁₁, C(═S)NR₁₀R₁₁, SO₂NR₁₀R₁₁, C(═NOR₉)R₈ or R₇; or R₁, R₂ and carbon atom linked to them form five, six or seven-membered ring;

R₇ is selected from unsubstituted or substituted phenyl, phenyloxy, phenyloxy C₁-C₁₂alkyl, phenylcarbonyl, phenyloxycarbonyl, phenylaminocarbonyl, phenylC₁-C₁₂alkyl, phenylC₁-C₁₂alkoxy, phenylC₁-C₁₂alkoxyC₁-C₁₂alkyl, naphthyl, naphthyloxy, naphthyloxy C₁-C₁₂alkyl, naphthylcarbonyl, naphthyl C₁-C₁₂alkyl, naphthyl C₁-C₁₂alkoxy, naphthyl C₁-C₁₂alkoxyC₁-C₁₂alkyl, heteroaryl, heteroaryloxy, heteroarylC₁-C₁₂alkoxyC₁-C₁₂alkyl, heteroaryloxyC₁-C₁₂alkyl, heteroarylcarbonyl, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylC₁-C₁₂alkyl or heteroarylC₁-C₁₂alkoxy, which is further mutually independently optionally substituted by 1 to 5 following group(s): halo, NO₂

CN, SH, C₁-C₆alkyl, C₁-C₆ halo alkyl, C₃-C₈cycloalkyl, C₁-C₆alkoxy, C₁-C₆ halo alkoxy, C₁-C₆alkylthio, C₁-C₆ halo alkylthio, C₂-C₆alkenyl, C₂-C₆ halo alkenyl, C₂-C₆alkynyl, halo alkynyl, C₃-C₆alkenyloxy, C₃-C₆ halo alkenyloxy, C₃-C₆alkynyloxy, C₃-C₆ halo alkynyloxy, C₁-C₆alkylsulfinyl, C₁-C₆ halo alkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆ halo alkylsulfonyl, C₁-C₆alkoxyC₁-C₆alkyl, C₁C₆alkylcarbonyl, C₁-C₆ halo alkylcarbonyl, C₁-C₆alkylcarbonyloxy, C₁-C₆alkylcarbonylamino, C₁-C₆alkylsulfonyloxy, C₁-C₆alkoxycarbonyl, C₁-C₆alkoxyC₁-C₆alkoxy, C₁-C₆alkoxycarbonylC₁-C₆alkyl, C₁-C₆alkoxycarbonylamino, C₁-C₆alkoxycarbonylC₁-C₆alkoxy, CHO, CO₂H, CO₂Na, CO₂NH₄, NR₁₀R₁₁, C(═O)NR₁₀R₁₁, OC(═O)NR₁₀R₁₁, C(═S)NR₁₀R₁₁ or SO₂NR₁₀R₁₁:

R₈, R₉ is mutually independently selected from H, C₁-C₆alkyl, aryl or aryl C₁-C₆ alkyl;

R₁₀, R₁₁ mutually independently may be the same or different, selected from H, C₁-C₆alkyl, C₁-C₆ halo alkyl, C₁-C₆alkoxy, C₁-C₆ halo alkoxy, C₁-C₆alkylthio, C₁-C₆ halo alkylthio or C₃-C₈cycloalkyl;

And their stereoisomers.

The preferred substituent benzyloxy group containing ether compounds above compounds applied as antitumor drugs of general formula I of this invention are:

Ar is selected from Ar1, Ar2, Ar3, Ar4 or Ar16;

Q is selected from Q₁, Q₂, Q₃, Q₄, Q₅, Q₆, Q₇, Q₈, Q₉, Q₁₉, Q₂₀, Q₂₁ or Q₂₂:

R₁, R₂, R₃, R₄, R₅, R₆ mutually independently may be the same or different, selected from H, halo, CN, NO₂, OH, NH₂, CHO, CO₂H, CO₂Na, CO₂NH₄, C₁-C₆alkyl, C₁-C₆haloalkyl, C₃-C₆cycloalkyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆haloalkylthio, C₁-C₆alkoxyC₁-C₆alkyl, haloC₁-C₆alkoxyC₁-C₆alkyl, C₁-C₆alkoxyC₁-C₆alkoxy, haloC₁-C₆alkoxyC₁-C₆alkoxy, C₁-C₆alkylthioC₁-C₆alkyl, haloC₁-C₆alkylthioC₁-C₆alkyl, C₁-C₆alkylamino, C₁-C₆haloalkylamino, C₂-C₈dialkylamino, C₂-C₈halodialkylamino, piperidinyl, pyrrolidinyl, N-methylpiperidinyl, morpholinyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₂-C₆alkenyloxy, C₂-C₆haloalkenyloxy, C₂-C₆alkynyloxy, C₂-C₆haloalkynyloxy, C₁-C₆alkylsulfonyl, C₁-C₆haloalkylsulfonyl, C₁-C₆alkylsulfinyl, C₁-C₆haloalkylsulfinyl, C₁-C₆alkylcarbonyl, C₁-C₆haloalkylcarbonyl, C₁-C₆alkylcarbonyloxyl, C₁-C₆alkylcarbonylamino, C₁-C₆alkylsulfonyloxy, C₁-C₆alkoxycarbonyl, C₁-C₆haloalkoxycarbonyl, C₁-C₆alkylaminosulfonyl, C₁-C₆alkoxycarbonylamino, C₁-C₆alkoxycarbonylC₁-C₆alkyl, C₁-C₆alkoxycarbonylC₁-C₆alkoxy, aminoC₁-C₆alkyl, C₁-C₆alkylaminoC₁-C₆alkyl, C₂-C₈dialkylaminoC₁-C₆alkyl, C(═0)NR₁₀R₁₁, OC(═O)NR₁₀R₁₁, C(═S)NR₁₀R₁₁, SO₂NR₁₀R₁₁, C(═NOR₉) R₈ or R₇; or R₁, R₂ and carbon atom linked to them form five or six-membered ring;

R₇ is selected from unsubstituted or substituted phenyl, phenyloxy, phenyloxy C₁-C₆alkyl, phenylcarbonyl, phenyloxycarbonyl, phenylaminocarbonyl, phenylC₁-C₆alkyl, phenylC₁-C₆alkoxy, phenylC₁-C₆alkoxyC₁-C₆alkyl, naphthyl, naphthyloxy, naphthyloxy C₁-C₆alkyl, naphthylcarbonyl, naphthyl C₁-C₆alkyl, naphthyl C₁-C₆alkoxy, naphthylC₁-C₆alkoxyC₁-C₆alkyl, heteroaryl, heteroaryloxy, heteroarylC₁-C₆alkoxyC₁-C₆alkyl, heteroaryloxyC₁-C₆alkyl, heteroarylcarbonyl, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylC₁-C₆alkyl or heteroarylC₁-C₆alkoxy, which is further mutually independently optionally substituted by 1 to 5 following group(s): halo, NO₂, SH, C₁-C₄alkyl, C₁-C₄ haloalkyl, C₃-C₆cycloalkyl, C₁-C₄alkoxy

C₁-C₄ halo alkoxy, C₁-C₄alkylthio, C₁-C₄ halo alkylthio, C₂-C₄alkenyl, C₂-C₄ halo alkenyl, C₂-C₄alkynyl, C₂-C₄ halo alkynyl, C₃-C₄alkenyloxy, C₃-C₄halo alkenyloxy, C₃-C₄alkynyloxy, C₃-C₄ halo alkynyloxy, C₁-C₄alkylsulfinyl, C₁-C₄ halo alkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄ halo alkylsulfonyl, C₁-C₄alkoxyC₁-C₄alkyl, C₁-C₄alkylcarbonyl, C₁-C₄ halo alkylcarbonyl, C₁-C₄alkylcarbonyloxy, C₁-C₄alkylcarbonylamino, C₁-C₄alkylsulfonyloxy, C₁-C₄alkoxycarbonyl, C₁-C₄alkoxyC₁-C₄alkoxy, C₁-C₄alkoxycarbonylC₁-C₄alkyl, C₁-C₄alkoxycarbonylamino, C₁-C₄alkoxycarbonylC₁-C₄alkoxy, CHO, CO₂H, CO₂Na, CO₂NH₄, NR₁₀R₁₁, C(═O)NR₁₀R₁₁, OC(═O)NR₁₀R₁₁, C(═S)NR₁₀R₁₁ or SO₂NR₁₀R₁₁:

R₈, R₉ is mutually independently selected from H, C₁-C₄alkyl, aryl or aryl C₁-C₄alkyl;

R₁₀, R₁₁ mutually independently may be the same or different, selected from C₁-C₄alkyl, C₁-C₄ halo alkyl, C₁-C₄alkoxy, C₁-C₄ halo alkoxy, C₁-C₄alkylthio, C₁-C₄ halo alkylthio or C₃-C₆cycloalkyl.

The preferred substituent benzyloxy group containing ether compounds above compounds applied as antitumor drugs of general formula I of this invention are:

Ar is selected from Ar1, Ar2, Ar3, Ar4 or Ar16;

Q is selected from Q₁, Q₂, Q₃, Q₄, Q₅, Q₆, Q₇, Q₈, Q₉, Q₁₉, Q₂₀, Q₂₁, or Q₂₂:

R₁, R₂, R₃, R₄, R₅, R₆ mutually independently may be the same or different, selected from H, halo, CN, NO₂, OH, NH₂, CHO, CO₂H, CO₂Na, CO₂NH₄, C₁-C₆alkyl, C₁-C₆haloalkyl, C₃-C₆cycloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₁-C₄alkylthio, C₁-C₄haloalkylthio, C₁-C₄alkoxyC₁-C₄alkyl, haloC₁-C₄alkoxyC₁-C₄alkyl, C₁-C₄alkoxyC₁-C₄alkoxy, haloC₁-C₄alkoxyC₁-C₄alkoxy, C₁-C₄alkylthioC₁-C₄alkyl, haloC₁-C₄alkylthioC₁-C₄alkyl, C₁-C₄alkylamino, C₁-C₄haloalkylamino, C₂-C₆dialkylamino, C₂-C₆halodialkylamino, piperidinyl, pyrrolidinyl, N-methylpiperidinyl, morpholinyl, C₂-C₄alkenyl, C₂-C₄haloalkenyl, C₂-C₄alkynyl, C₂-C₄haloalkynyl, C₂-C₄alkenyloxy, C₂-C₄haloalkenyloxy, C₂-C₄alkynyloxy, C₂-C₄haloalkynyloxy, C₁-C₄alkylsulfonyl, C₁-C₄haloalkylsulfonyl, C₁-C₄alkylsulfinyl, C₁-C₄haloalkylsulfinyl, C₁-C₄alkylcarbonyl, C₁-C₄haloalkylcarbonyl, C₁-C₄alkylcarbonyloxy, C₁-C₄alkylcarbonylamino, C₁-C₄alkylsulfonyloxy, C₁-C₄alkoxycarbonyl, C₁-C₄haloalkoxycarbonyl, C₁-C₄alkylaminosulfonyl, C₁-C₄alkoxycarbonylamino, C₁-C₄alkoxycarbonylC₁-C₄alkyl, C₁-C₄alkoxycarbonylC₁-C₄alkoxy, aminoC₁-C₄alkyl, C₁-C₄alkylaminoC₁-C₄alkyl, C₂-C₆dialkylaminoC₁-C₄alkyl, C(═O)NR₁₀R₁₁, OC(═O)NR₁₀R₁₁, C(═S)NR₁₀R₁₁, SO₂NR₁₀R₁₁, C(═NOR₉)R₈ or R₇; or R₁, R₂ and carbon atom linked to them form saturated five or six-membered ring;

R₇ is selected from unsubstituted or substituted phenyl, phenyloxy, phenyloxy C₁-C₄alkyl, phenylcarbonyl, phenyloxycarbonyl, phenylaminocarbonyl, phenylC₁-C₄alkyl, phenylC₁-C₄alkoxy, phenylC₁-C₄alkoxyC₁-C₄alkyl, naphthyl, naphthyloxy, naphthyloxy C₁-C₄alkyl, naphthylcarbonyl, naphthyl C₁-C₄alkyl, naphthyl C₁-C₄alkoxy, naphthylC₁-C₄alkoxyC₁-C₄alkyl, heteroaryl, heteroaryloxy, heteroarylC₁-C₄alkoxyC₁-C₄alkyl, heteroaryloxyC₁-C₄alkyl, heteroarylcarbonyl, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylC₁-C₄alkyl or heteroarylC₁-C₄alkoxy, which is further mutually independently optionally substituted by 1 to 5 following group(s): halo, NO₂, CN, SH, C₁-C₄alkyl, C₁-C₄ haloalkyl, C₃-C₆cycloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₁-C₄alkylthio, C₁-C₄ halo alkylthio, C₂-C₄alkenyl, C₂-C₄ halo alkenyl, C₂-C₄alkynyl, C₂-C₄ halo alkynyl, C₃-C₄alkenyloxy, C₃-C₄halo alkenyloxy, C₃-C₄alkynyloxy, C₃-C₄ haloalkynyloxy, C₁-C₄alkylsulfinyl, C₁-C₄ halo alkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄ halo alkylsulfonyl, C₁-C₄alkoxyC₁-C₄alkyl, C₁-C₄alkylcarbonyl, C₁-C₄ halo alkylcarbonyl, C₁-C₄alkylcarbonyloxy, C₁-C₄alkylcarbonylamino, C₁-C₄alkylsulfonyloxy, C₁-C₄alkoxycarbonyl, C₁-C₄alkoxyC₁-C₄alkoxy, C₁-C₄alkoxycarbonylC₁-C₄alkyl, C₁-C₄alkoxycarbonylamino, C₁-C₄alkoxycarbonylC₁-C₄alkoxy, CHO, CO₂H, CO₂Na, CO₂NH₄, NR₁₀R₁₁, C(═O)NR₁₀R₁₁, OC(═O)NR₁₀R₁₁, C(═S)NR₁₀R₁₁ or SO₂NR₁₀R₁₁:

R₈, R₉ is mutually independently selected from H, C₁-C₄alkyl, aryl or aryl C₁-C₄alkyl;

R₁₀, R₁₁ mutually independently may be the same or different, selected from H, C₁-C₄alkyl, C₁-C₄ haloalkyl, C₁-C₄alkoxyl

C₁-C₄ haloalkoxy, C₁-C₄alkylthio, C₁-C₄ haloalkylthio or C₃-C₆cycloalkyl.

Furthermore, the preferred substituent benzyloxy group containing ether compounds above compounds applied as antitumor drugs of general formula I of this invention are:

Ar is selected from Ar1, Ar2, Ar3 or Ar16;

Q is selected from Q₁, Q₂, Q₃, Q₄, Q₅, Q₆, Q₇ or Q₈;

R₁, R₂, R₃, R₄, R₅, R₆ mutually independently may be the same or different, selected from H, halo, CN, C₁-C₆alkyl, C₁-C₄haloalkyl, C₃-C₆cycloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₁-C₄alkylthio, C₁-C₄alkoxyC₁-C₄alkyl, C₁-C₄alkylamino, C₂-C₆dialkylamino, C₁-C₄alkylsulfonyl or R₇; or R₁, R₂ and carbon atom linked to them form saturated five or six-membered ring;

-   -   R₇ is selected from unsubstituted or substituted phenyl, benzyl,         phenylethyl or heteroaryl, which is further mutually         independently optionally substituted by 1 to 5 following         group(s): halo, NO₂, CN, C₁-C₄alkyl, C₁-C₄ haloalkyl,         C₁-C₄alkoxy or C₁-C₄ haloalkoxy.

Furthermore, the preferred substituent benzyloxy group containing ether compounds above compounds applied as antitumor drugs of general formula I of this invention are:

Ar is selected from Ar1, Ar2, Ar3 or Ar16;

Q is Q₁;

R₁, R₂, R₃, R₄, R₅, R₆ mutually independently may be the same or different, selected from H, halo, CN, C₁-C₆alkyl, C₁-C₄haloalkyl or R₇; or R₁, R₂ and carbon atom linked to them form saturated five or six-membered ring;

-   -   R₇ is selected from unsubstituted or substituted phenyl, benzyl         or heteroaryl, which is further mutually independently         optionally substituted by 1 to 5 following group(s): halo, NO₂,         CN, C₁-C₄alkyl, C₁-C₄ haloalkyl, C₁-C₄alkoxy or C₁-C₄         haloalkoxy.

Furthermore, the preferred substituent benzyloxy group containing ether compounds above compounds applied as antitumor drugs of general formula I of this invention are:

Ar is selected from Ar3 or Ar16;

Q is Q₁;

R₁, R₂, R₃, R₄, R₅, R₆ mutually independently may be the same or different, selected from H, halo, CN, C₁-C₆alkyl, C₁-C₄haloalkyl or R₇; or R₁, R₂ and carbon atom linked to them form saturated five or six-membered ring;

-   -   R₇ is selected from unsubstituted or substituted phenyl, benzyl         or heteroaryl, which is further mutually independently         optionally substituted by 1 to 5 following group(s): halo, NO₂,         CN, C₁-C₄alkyl, C₁-C₄ haloalkyl, C₁-C₄alkoxy or C₁-C₄         haloalkoxy.

Furthermore, the preferred substituent benzyloxy group containing ether compounds above compounds applied as antitumor drugs of general formula I of this invention are:

-   -   Ar is selected from Ar3 or Ar16;     -   Q is Q₁;     -   R₁ is selected from H, halo or C₁-C₆alkyl;     -   R₂ is selected from C₁-C₄alkyl, C₁-C₄haloalkyl or R₇;     -   Or R₁, R₂ and carbon atom linked to them form saturated five or         six-membered ring;     -   R₃, R₄ are H;     -   R₆ is selected from H or C₁-C₄alkyl;     -   R₇ is selected from unsubstituted or substituted phenyl, which         is further mutually independently optionally substituted by 1 to         3 following group(s); halo, CN, C₁-C₄alkyl, C₁-C₄ haloalkyl,         C₁-C₄alkoxy or C₁-C₄ haloalkoxy.

Furthermore, the preferred substituent benzyloxy group containing ether compounds above compounds applied as antitumor drugs of general formula I of this invention are:

-   -   Ar is selected from Ar3 or Ar16;     -   Q is Q₁;     -   R₁ is selected from H, halo or C₁-C₆alkyl;     -   R₂ is selected from C₁-C₄alkyl or R₇;     -   Or R₁, R₂ and carbon atom linked to them form saturated five or         six-membered ring;     -   R₃, R₄ are H;     -   R₆ is selected from H or C₁-C₄alkyl;     -   R₇ is selected from unsubstituted or substituted phenyl, which         is further mutually independently optionally substituted by 1 to         3 following group(s): halo, C₁-C₄alkyl, C₁-C₄alkoxy or C₁-C₄         haloalkoxy.

The more preferred substituent benzyloxy group containing ether compounds above compounds applied as antitumor drugs of general formula I of this invention are:

-   -   Ar is selected from Ar3 or Ar16;     -   Q is Q₁;     -   R₁ is selected from H, F or C₁-C₄alkyl;     -   R₂ is selected from C₁-C₄alkyl or phenyl;     -   Or R₁, R₂ and carbon atom linked to them form saturated         six-membered ring;     -   R₃, R₄ are H;     -   R₆ is selected from H or CH₃.

The most preferred substituent benzyloxy group containing ether compounds applied as antitumor drugs of general formula I of this invention are:

-   -   Ar is selected from Ar3 or Ar16;     -   Q is Q₁;     -   R₁ is selected from H or C₁-C₄alkyl;     -   R₂ is selected from CH₃ or phenyl;     -   Or R₁, R₂ and carbon atom linked to them form saturated         six-membered ring;     -   R₃, R₄, R₆ are H.

The terms used above to definite the compounds of general formula I represent substitutes as follow:

The “halogen” or “halo” is fluorine, chlorine, bromine or iodine.

The “alkyl” stands for straight or branched chain alkyl, such as methyl, ethyl, propyl, isopropyl or tert-butyl. The “haloalkyl” stands for straight or branched chain alkyl, in which hydrogen atoms can be all or partly substituted with halogen, such as chloromethyl, dichloromethyl, trichlororaethyl, fluoromethyl, difluoromethyl, trifluoromethyl, etc.

The “alkoxy” refers to straight or branched chain alkyl, which is linked to the structure by oxygen atom. The “haloalkoxy” refers to straight or branched chain alkoxy, in which hydrogen atoms may be all or partly substituted with halogen, such as chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, trifluoroethoxy, etc.

The “alkylthio” refers to straight or branched chain alkyl, which is linked to the structure by sulfur atom. The “haloalkylthio” refers to straight or branched chain alkylthio, in which hydrogen atoms may be all or partly substituted with halogen, such as chloromethylthio, dichloromethylthio, trichloromethylthio, fluoromethylthio, difluoromethylthio, trifluoromethylthio, chlorofluoromethylthio, etc.

The “alkoxyalkyl” means alkoxy is linked to the structure by alkyl. Such as —CH₂OCH₂, —CH₂OCH₂CH₃.

The “haloalkoxyalkyl” refers to alkoxyalkyl, in which hydrogen atoms may be all or partly substituted with halogen, such as —CH₂OCH₂CH₂Cl.

The “alkoxyalkoxy” means OCH₂OCH₂CH₃ etc. The “haloalkoxyalkoxy” means —OCH₂OCH₂CH₂Cl etc.

The “alkylthioalkyl” means alkylthio is linked to the structure by alkyl. Such as —CH₂SCH₂.

The “haloalkylthioalkyl” means haloalkylthio is linked to the structure by alkyl.

The “alkylamino” refers to straight or branched chain alkyl, which is linked to the structure by nitrogen atom.

The “haloalkylamino” refers to straight or branched chain alkylamino, in which hydrogen atoms may be all or partly substituted with halogen.

The alkenyl refers to straight or branched chain alkenyl, such as ethenyl, 1-propenyl, 2-propenyl and different isomer of butenyl, pentenyl and hexenyl. Alkenyl also includes polyene, such as propa-1,2-dienyl and hexa-2,4-dienyl. The haloalkenyl stands for straight or branched chain alkenyl, in which hydrogen atoms can be all or partly substituted with halogen. The alkynyl refers to straight or branched chain alkynyl, such as ethynyl, 1-propynyl and different isomer of butynyl, pentynyl and hexynyl. Alkynyl also includes groups including more than one triple bonds, such as hexa-2,5-diynyl. The “haloalkynyl” stands for straight or branched chain alkynyl, in which hydrogen atoms can be all or partly substituted with halogen.

The alkenoxyl refers to straight or branched chain alkynes is linked to the structure by oxygen, such as propenyloxy. The haloalkenoxyl stands for a straight-chain or branched alkenoxyl, in which hydrogen atoms may be all or partly substituted with halogen. The alkynoxyl refers to straight or branched chain alkynes is linked to the structure by oxygen, such as propynyloxy. The haloalkynoxyl stands for a straight-chain or branched alkynoxyl, in which hydrogen atoms may be all or partly substituted with halogen.

The “alkylsulfonyl” means a straight-chain or branched alkyl is linked to the structure by (—SO₂—), such as methylsulfonyl. The “haloalkylsulfonyl” stands for a straight-chain or branched alkylsulfonyl, in which hydrogen atoms may be all or partly substituted with halogen.

The “alkylsulfinyl” means a straight-chain or branched alkyl is linked to the structure by (—SO—), such as methylsulfinyl.

The “haloalkylsulfinyl” stands for a straight-chain or branched alkylsulfinyl, in which hydrogen atoms may be all or partly substituted with halogen.

The “alkylcarbonyl” means alkyl is linked to the structure by carbonyl. such as CH₃CO—, CH₃CH₂CO—.

The “haloalkylcarbonyl” stands for a straight-chain or branched alkylcarbonyl, in which hydrogen atoms may be all or partly substituted with halogen, such as CF₃CO—.

The “alkylcarbonyloxy” means CH₃COO—, CH₃CH₂NHCOO— etc. The “alkylcarbonylamino” means CH₃CONH—, CH₃CH₂NHCONH— etc.

The “alkylsulfonyloxy” means alkyl-S(O)₂—O—. The “alkoxycarbonyl” means alkyl-O—CO—.

The “haloalkoxycarbonyl” stands for alkoxycarbonyl, in which hydrogen atoms can be all or partly substituted with halogen, such as —COOCH₂CF₃, —COOCH₂CH₂Cl.

The “alkylaminosulfonyl” means —S(O)₂NHCH₃, —S(O)₂NHCH₂CH₃ etc. The “alkoxycarbonylamino” means —NHCOOCH₃, —NHCOOCH₂CH₃ etc. The “alkoxycarbonylalkyl” means —CH₂COOCH₃, —CH₂COOCH₂CH₃ etc. The “alkoxycarbonylalkoxy” means —OCH₂COOCH₃, —OCH₂COOCH₂CH₃ etc. The “aminoalkyl” such as —CH₂NH₂, —CH₂CH₂NH₂. The “alkylaminoalkyl” such as CH₂NHCH₃, —CH₂NHCH₂CH₃. The “dialkylaminoalkyl” such as —CH₂NH(CH₃)₂ etc.

The “aryl” in terms of (hetero)aryl, (hetero)aryloxy, (hetero)arylalkoxyalkyl, (hetero)aryloxyalkyl, (hetero)arylcarbonyl, (hetero)aryloxycarbonyl, (hetero)arylaminocarbonyl, (hetero)arylalkyl or (hetero)arylalkoxy include phenyl or naphthyl etc.

The heteroaryl stands for five member ring or six member ring containing one or more N, O, S hetero atoms. Such as pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furyl, thiazolyl, quinolinyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrazolyl, pyranyl, triazolyl, tetrazolyl, benzothiazolyl, benzofuranyl, etc. The (hetero)aryloxy such as phenyloxy, pyridinyloxy, pyrimidinyloxy, quinolinyloxy, eye.

The (hetero)arylalkoxyalkyl means —CH₂OCH₂Ph, 6-chloropyridin-3-ylmethoxyl, etc. The (hetero)aryloxyalkyl means, —CH₂OPh, 4,6-(OCH₃)₂-2-yloxyethyl, etc. The (hetero)arylcarbonyl means PhCHO, 4-ClPhCHO, etc. The (hetero)aryloxycarbonyl means PhOCO, 4-ClPhOCO, 4-NO₂PhOCO, Naph OCO, etc. The (hetero)arylaminocarbonyl, (hetero)arylalkyl or (hetero)arylalkoxy includes phenyl or naphthyl etc.

The compounds of the present invention can form stereoisom (Z- and E-isomer respectively) due to the existing of C═C and C═N bonds. The invention includes Z-isomer and E-isomer and their mixture at any ratio.

The drugs were made from the active ingredients of general formula I substituent benzyloxy group containing ether compounds, which can dose by oral medication or parenteral route, also by implantable medication pump and other methods.

The substituent benzyloxy group containing ether compounds having the general formula I in present invention can be used to prepare the drugs for curing or alleviating the cancer. The formulations include tablets, pills, capsule, granule, syrup, injection or freeze-dried powder injection.

Furthermore, the substituent benzyloxy group containing ether compounds having the general formula I in present invention can be used to cure or alleviate the cancer causing by cancer cells of human tissue or organ. The cancers include but not limited to colon cancer, liver cancer, lymph cancer, lung cancer, esophageal cancer, breast cancer, central nervous system cancer, melanoma, ovarian cancer, cervical cancer, renal cancer, leukemia, prostatic cancer, pancreatic cancer, bladder cancer, rectal cancer or stomach cancer.

Part of the substitutes of R₁, R₂, R₃, R₄, R₅ and R₆ in formula I are seperately listed in table 1, but without being restricted thereby.

TABLE 1 substitute R₁ (R₂, R₃, R₄, R₅, R₆) R₁ (R₂, R₃, R₄, R₁ (R₂, R₃, R₄, R₁ (R₂, R₃, R₄, R₅, R₅, R₆) R₅, R₆) R₆) R₁ (R₂, R₃, R₄, R₅, R₆) H NH(CH₂)₃CH₃ OCONHCH₂CH₃ Ph-2,3-2CN-4,5,6-3Cl F NHC(CH₃)₃ OCON(CH₂CH₃)₂ Ph-2,3-2CN-3,5,6-3Cl Cl

OCONH(CH₂)₂CH₃ OPh Br

OCONHCH(CH₃)₂ CONHPh-2-Cl-4-CF₃ I

OCONH(CH₂)₃CH₃ CONHPh-2-Cl-4-NO₂ CN

OCONHC(CH₃)₃ CH₂Ph NO₂ CH₂CH═CH₂ CSNH₂ CH₂—Ph-4-Cl OH CH₂CH═CF₂ CSNHCH₃ CH₂CH₂Ph NH₂ CH₂CH₂CH═CF₂ CSN(CH₃)₂ CH₂CH₂—Ph-4-Cl CHO CH₂CH₂CF═CF₂ CSNHCH₂CH₃ OCH₂Ph COOH CH₂CH═CCl₂ CSN(CH₂CH₃)₂ OCH₂CH₂Ph CO₂Na CH₂C≡CH CSNH(CH₂)₂CH₃ CH₂OCH₂Ph CO₂NH₄ CH₂C≡C—I CSNHCH(CH₃)₂ CH₂OCH₂CH₂Ph CH₃ CH₂C≡C—Cl CSNH(CH₂)₃CH₃ CH₂OPh CH₂CH₃ CH₂C≡CCH₃ CSNHC(CH₃)₃ naphthyloxy n-C₃H₇ OCH₂CH═CH₂ SO₂NH₂ naphthylmethyl i-C₃H₇ OCH₂CH═CCl₂ SO₂NHCH₃ 6-chloropyridin-3-yl i-C₃H₇CH₂CH₂ OCH₂C≡CH SO₂N(CH₃)₂ 3-Cl-5-CF₃-pyridin-2-yl n-C₄H₉ SO₂CH₃ C(═NOCH₃)CH₃ 5-CF₃-pyridin-2-yl i-C₄H₉ SO₂CH₂CH₃ Ph 3,5,6-Cl₃-pyridin-2-yl n-C₅H₁₁ SOCH₃ Ph-2-F 3,5-Cl₂-pyridin-2-yl n-C₆H₁₃ SOCH₃CH₃ Ph-3-F 5-OCF₃-pyridin-2-yl CH₂Bu-t COCH₃ Ph-4-F 6-Cl-pyridazin-3-yl CF₃ COCH₂CH₃ Ph-2-Cl 6-CF₃-pyridazin-3-yl CHF₂ COCF₃ Ph-3-Cl 6-OCF₃-pyridazin-3-yl CH₂F COCH₂Cl Ph-4-Cl 3-Cl-pyrazin-2-y CH₂Cl COCH₂CH₂Cl Ph-4-CH₃ 6-Cl-pyrazin-2-y CH₂Br OCOCH₃ Ph-3-CH₃ pyrimidin-2-yl CH₂CF₃ OCOCH₂CH₃ Ph-2-OCH₃ pyrimidin-4-yl CF₂CHF₂ NHCOCH₃ Ph-3-OCH₃ pyrimidin-5-yl CF₂CF₃ NHCOCH₂CH₃ Ph-4-OCH₃ 5-Cl-pyrimidin-2-yl

OSO₂CH₃ Ph-2-CF₃ 5-CF₃-pyrimidin-2-yl

OSO₂CH₂CH₃ Ph-3-CF₃ 5-OCH₃—CO-pyridin-2-yl

CO₂CH₃ Ph-4-CF₃ 4,6-(CH₃)₂-pyrimidin-2-yl OCH₃ CO₂CH₂CH₃ Ph-2-OCF₃ 4,6-(OCH₃)₂-pyrimidin-2-yl OCH₂CH₃ CO₂CH₂CH₂Cl Ph-3-OCF₃ 4,6-(CH₃)₂-triazin-2-yl O(CH₂)₂CH₃ SO₂NH₂ Ph-4-OCF₃ 4,6-(OCH₃)₂-triazin-2-yl OCH(CH₃)₂ SO₂NHCH₃ Ph-4-NO₂ 5-Cl-benzoxazol-2-yl OCF₃ SO₂N(CH₃)₂ Ph-4-CN 6-Cl-quinoxalin-2-yl OCH₂CF₃ NHCOOCH₃ Ph-4-t-Bu 4-CH₃-benzyl OCF₂CF₃ NHCOOCH₂CH₃ Ph-2,4-2Cl 2-CN-benzyl SCH₃ CH₂CO₂CH₃ Ph-2,4-2F 2-Cl-6-F-benzyl CH₂OCH₃ CH₂CO₂CH₂CH₃ Ph-3,5-2Cl 2,5-Cl₂-benzyl CH₂OCH₂CH₃ OCH₂CO₂CH₃ Ph-3,4-2Cl 6-Cl-pyridin-3-ylmethyl CH₂OCH₂Cl CH₂NHCH₃ Ph-2,3-2Cl 2-Ck-thiazol-5-ylmethyl CH₂OCH₂CHF₂ CH₂N(CH₃)₂ Ph-2,5-2Cl benzoxazol-2-yloxy CH₂OCH₂CF₃ CONH₂ Ph-2,6-2Cl 5-Cl-benzoxazol-2-ylmethyl CH₂SCH₃ CONHCH₃ Ph-2-CH₃-4-Cl 3-Cl-5-CF₃-pyridin-2-yloxy CH₂SCH₂CH₃ CON(CH₃)₂ Ph-2-Cl-4-CF₃ 6-Cl-pyridn-3-ylmethoxyl CH₂SCH₂Cl CONHCH₂CH₃ Ph-3,4-(OMe)₂ 2-Cl-thiazol-5-ylmethoxy CH₂SCH₂CHF₂ CON(CH₂CH₃)₂ Ph-2,6-2Cl-4-CF₃ 5-CH₂Cl-pyridin-2-yloxymethyl NHCH₃ CONH(CH₂)₂CH₃ Ph-2,6-2Cl-4-NO₂ 6-Cl-pyridin-3-ylmethoxymethyl N(CH₃)₂ CONHCH(CH₃)₂ Ph-2,4,6-3Cl 6-Cl-pyridn-3-yl(C═O) NHCH₂CH₃ CONH(CH₂)₃CH₃ Ph-2,4,6-3CH₃ pyridn-2-ylO(C═O) N(CH₂CH₃)₂ CONHC(CH₃)₃ Ph-2-CH₃-3-Cl-4,6-2NO₂ pyridn-3-yl NH(C═O) NH(CH₂)₂CH₃ OCONHCH₃ Ph-3-Cl-2,6-2NO₂-4-CF₃ NHCH(CH₃)₂ OCON(CH₃)₂ Ph-2,5-2CN-3,4,6-3Cl R₁, R₂ CH₂CH₂CH₂ CH₂CH₂CH₂CH₂ CH₂CH₂CH₂CH₂CH₂

The present invention is also explained by the following compounds having general formula I with antitumor activity in Table 2-Table 53, but without being restricted thereby.

When Ar is Ar1, Q is Q₁, the presentitive compounds 2-1 to 2-112 are listed in Table 2.

TABLE 2 substituents when Ar = Ar1

No. R₁ R₃ R₄ R₅ R₆ 2-1 H H H H H 2-2 CH₃ H H H H 2-3 C₂H₅ H H H H 2-4 i-C₃H₇ H H H H 2-5 n-C₃H₇ H H H H 2-6 n-C₄H₉ H H H H 2-7 t-C₄H₉ H H H H 2-8 OCH₃ H H H H 2-9 OC₂H₅ H H H H 2-10 CH₂Cl H H H H 2-11 CH₂NH₂ H H H H 2-12 CH₂CH₂NH₂ H H H H 2-13 CH₂CH₂CN H H H H 2-14 NH₂ H H H H 2-15 NO₂ H H H H 2-16 OH H H H H 2-17 CO₂H H H H H 2-18 F H H H H 2-19 Cl H H H H 2-20 Br H H H H 2-21 I H H H H 2-22 CH₂—CH═CH₂ H H H H 2-38 CH₂—C≡CH H H H H 2-39 H CH₃ H H H 2-40 H C₂H₅ H H H 2-41 H i-C₃H₇ H H H 2-42 H n-C₃H₇ H H H 2-43 H n-C₄H₉ H H H 2-44 H t-C₄H₉ H H H 2-45 H OCH₃ H H H 2-46 H OC₂H₅ H H H 2-47 H CH₂Cl H H H 2-48 H CO₂H H H H 2-49 H F H H H 2-50 H Cl H H H 2-51 H Br H H H 2-52 H I H H H 2-53 H Ph H H H 2-54 H H CH₃ H H 2-55 H H C₂H₅ H H 2-56 H H i-C₃H₇ H H 2-57 H H n-C₃H₇ H H 2-58 H H n-C₄H₉ H H 2-59 H H t-C₄H₉ H H 2-60 H H OCH₃ H H 2-61 H H OC₂H₅ H H 2-62 H H NH₂ H H 2-63 H H OH H H 2-64 H H CO₂H H H 2-65 H H F H H 2-66 H H Cl H H 2-67 H H Br H H 2-68 H H I H H 2-69 H H Ph H H 2-70 H H H CH₃ H 2-71 H H H C₂H₅ H 2-72 H H H i-C₃H₇ H 2-73 H H H n-C₃H₇ H 2-74 H H H n-C₄H₉ H 2-75 H7 H H t-C₄H₉ H 2-76 H H H OCH₃ H 2-77 H H H OC₂H₅ H 2-78 H H H CH₂Cl H 2-79 H H H N(CH₃)₂ H 2-80 H H H OCOOCH₃ H 2-81 H H H OCOCH₃ H 2-82 H H H NH₂ H 2-83 H H H CN H 2-84 H H H OH H 2-85 H H H CO₂H H 2-86 H H H F H 2-87 H H H Cl H 2-88 H H H Br H 2-89 H H H I H 2-90 H H H CH₂—CH═CH₂ H 2-91 H H H CH₂—C≡CH H 2-92 H H H H CH₃ 2-93 H H H H C₂H₅ 2-94 H H H H OCH₃ 2-95 H H H H CHO 2-96 H H H H F 2-97 H H H H Cl 2-98 H H H H Br 2-99 H H H H I 2-100 H H H H Ph 2-101 H H H H CH₂Ph 2-102 CH₃ H H H CH₃ 2-103 H H CH₃ CH₃ H 2-104 H H CH₃ H CH₃ 2-105 H H OCH₃ H OCH₃ 2-106 H H Cl H Cl 2-107 H H H CH₃ CH₃ 2-108 CH₃ H H CH₃ H 2-109 H H Cl CH₃ H 2-110 H H C₂H₅ C₂H₅ H 2-111 CH₃ H CH₃ H H 2-112 H CH₃ CH₃ H CH₃

Table 3: When Ar is Ar1, Q is Q₂, the substituents of presentitive compounds 3-1 to 3-112 are consistent with 2-1 to 2-112 in Table 2;

Table 4: When Ar is Ar1, Q is Q₃, the substituents of presentitive compounds 4-1 to 4-112 are consistent with 2-1 to 2-112 in Table 2;

Table 5: When Ar is Ar1, Q is Q₄, the substituents of presentitive compounds 5-1 to 5-112 are consistent with 2-1 to 2-112 in Table 2;

Table 6: When Ar is Ar1, Q is Q₅, the substituents of presentitive compounds 6-1 to 6-112 are consistent with 2-1 to 2-112 in Table 2;

Table 7: When Ar is Ar1, Q is Q₆, the substituents of presentitive compounds 7-1 to 7-112 are consistent with 2-1 to 2-112 in Table 2;

Table 8: When Ar is Ar1, Q is Q₇, the substituents of presentitive compounds 8-1 to 8-112 are consistent with 2-1 to 2-112 in Table 2;

Table 9: When Ar is Ar1, Q is Q₈ is the substituents of presentitive compounds 9-1 to 9-112 are consistent with 2-1 to 2-112 in Table 2;

Table 10: When Ar is Ar1, Q is Q₉, the substituents of presentitive compounds 10-1 to 10-112 are consistent with 2-1 to 2-112 in Table 2;

Table 11: When Ar is Ar1, Q is Q₁₉, the substituents of presentitive compounds 11-1 to 11-112 are consistent with 2-1 to 2-112 in Table 2;

Table 12: When Ar is Ar1, Q is Q₂₀, the substituents of presentitive compounds 12-1 to 12-112 are consistent with 2-1 to 2-112 in Table 2;

Table 13: When Ar is Ar1, Q is Q21, the substituents of presentitive compounds 13-1 to 13-112 are consistent with 2-1 to 2-112 in Table 2;

Table 14: When Ar is Ar1, Q is Q₂₂, the substituents of presentitive compounds 14-1 to 14-112 are consistent with 2-1 to 2-112 in Table 2.

When Ar is Ar2, Q is Q₁, the presentitive compounds 15-1 to 15-121 are listed in Table 15.

TABLE 15 substituents when Ar = Ar2

No. R₁ R₂ R₃ R₅ R₆ 15-1 H H H H H 15-2 CH₃ H H H H 15-3 C₂H₅ H H H H 15-4 i-C₃H₇ H H H H 15-5 n-C₃H₇ H H H H 15-6 n-C₄H₉ H H H H 15-7 t-C₄H₉ H H H H 15-8 OH H H H H 15-9 NH₂ H H H H 15-10 CN H H H H 15-11 NO₂ H H H H 15-12 CHO H H H H 15-13 CO₂H H H H H 15-14 COCH₃ H H H H 15-15 CONH₂ H H H H 15-16 COOCH₃ H H H H 15-17 CH₂COCH₃ H H H H 15-18 CH₂—CH═CH₂ H H H H 15-19 C(CH₃)₂—CH═CH₂ H H H H 15-20 4-Cl—Ph H H H H 15-21 4-CH₃—Ph H H H H 15-22 H CH₃ H H H 15-23 H C₂H₅ H H H 15-24 H i-C₃H₇ H H H 15-25 H n-C₃H₇ H H H 15-26 H n-C₄H₉ H H H 15-27 H t-C₄H₉ H H H 15-28 H OCH₃ H H H 15-29 H OC₂H₅ H H H 15-30 H CH₂Cl H H H 15-31 H CH₂NH₂ H H H 15-32 H CH₂CH₂NH₂ H H H 15-33 H COOCH₃ H H H 15-34 H COCH₃ H H H 15-35 H CH₂COCH₃ H H H 15-36 H OH H H H 15-37 H 4-t-C₄H₉—Ph H H H 15-38 H 4-Cl—Ph H H H 15-39 H 4-CH₃—Ph H H H 15-40 H H CH₃ H H 15-41 H H C₂H₅ H H 15-42 H H i-C₃H₇ H H 15-43 H H n-C₃H₇ H H 15-44 H H n-C₄H₉ H H 15-45 H H t-C₄H₉ H H 15-46 H H OH H H 15-47 H H NH₂ H H 15-48 H H CN H H 15-49 H H NO₂ H H 15-50 H H CHO H H 15-51 H H CO₂H H H 15-52 H H COCH₃ H H 15-53 H H CH₂N(CH₃)₂ H H 15-54 H H CH₂—CH═CH₂ H H 15-55 H H C(CH₃)₂—CH═CH₂ H H 15-56 H H F H H 15-57 H H Cl H H 15-58 H H Br H H 15-59 H H I H H 15-60 H H H CH₃ H 15-61 H H H C₂H₅ H 15-62 H H H i-C₃H₇ H 15-63 H H H n-C₃H₇ H 15-64 H H H n-C₄H₉ H 15-65 H H H t-C₄H₉ H 15-66 H H H OCH₃ H 15-67 H H H OC₂H₅ H 15-68 H H H CH₂Cl H 15-69 H H H COCH₃ H 15-70 H H H NH₂ H 15-71 H H H NO₂ H 15-72 H H H OH H 15-73 H H H OCOCH₃ H 15-74 H H H F H 15-75 H H H Cl H 15-76 H H H Br H 15-77 H H H I H 15-78 H H H CH₂—CH═CH₂ H 15-79 H H H CH₂—C≡CH H 15-80 H H H H CH₃ 15-81 H H H H C₂H₅ 15-82 H H H H i-C₃H₇ 15-83 H H H H n-C₃H₇ 15-84 H H H H n-C₄H₉ 15-85 H H H H t-C₄H₉ 15-86 H H H H OCH₃ 15-87 H H H H OC₂H₅ 15-88 H H H H OH 15-89 H H H H C(NOCH₃)CH₃ 15-90 H H H H F 15-91 H H H H Cl 15-92 H H H H Br 15-93 H H H H I 15-94 H H H H CH₂—CH═C(CH₃)₂ 15-95 H CH₃ H H CH₃ 15-96 H Ph H H CH₃ 15-97 H Ph H H OCH₃ 15-98 H CH₂Cl H H Ph 15-99 H H CH₃ H CH₃ 15-100 H H OCH₃ H OCH₃ 15-101 CH₃ H H OCH₃ H 15-102 CH₃ H H CH═CH₂Ph H 15-103 H CH₃ CH₃ H H 15-104 CH₃ CH₃ H H H 15-105 Ph CH₃ H H H 15-106 H CH₃ OCH₃ H H 15-107 H CH₃ Cl H H 15-108 H CH₃ H H t-C₄H₉ 15-109 H H H OCH₃ OCH₃ 15-110 H H CH₃ CH₃ CH₃ 15-111 H CH₃ H CH₃ CH₃ 15-112 CH₃ CH₃ H CH₃ H 15-113 H H OCH₃ OCH₃ OCH₃ 15-114 CH₂CH₂CH₂ H H H 15-115 CH₂CH₂CH₂ H H CH₃ 15-116 CH₂CH₂CH₂ H CH₃ H 15-117 CH₂CH₂CH₂ H Ph H 15-118 CH₂CH₂CH₂CH₂ H H H 15-119 CH₂CH₂CH₂CH₂ H H CH₃ 15-120 CH₂CH₂CH₂CH₂ H CH₃ H 15-121 CH₂CH₂CH₂CH₂ H Ph H

Table 16: When Ar is Ar2, Q is Q₂, the substituents of presentitive compounds 16-1 to 16-121 are consistent with 15-1 to 15-121 in Table 15;

Table 17: When Ar is Ar2, Q is Q₃, the substituents of presentitive compounds 17-1 to 17-121 are consistent with 15-1 to 15-121 in Table 15;

Table 18: When Ar is Ar2, Q is Q₄, the substituents of presentitive compounds 18-1 to 18-121 are consistent with 15-1 to 15-121 in Table 15;

Table 19: When Ar is Ar2, Q is Q₅, the substituents of presentitive compounds 19-1 to 19-121 are consistent with 15-1 to 15-121 in Table 15;

Table 20: When Ar is Ar2, Q is Q₆, the substituents of presentitive compounds 20-1 to 20-121 are consistent with 15-1 to 15-121 in Table 15;

Table 21: When Ar is Ar2, Q is Q₇, the substituents of presentitive compounds 21-1 to 21-121 are consistent with 15-1 to 15-121 in Table 15;

Table 22: When Ar is Ar2, Q is Q₈, the substituents of presentitive compounds 22-1 to 22-121 are consistent with 15-1 to 15-121 in Table 15;

Table 23: When Ar is Ar2, Q is Q₉, the substituents of presentitive compounds 23-1 to 23-121 are consistent with 15-1 to 15-121 in Table 15;

Table 24: When Ar is Ar2, Q is Q₁₉, the substituents of presentitive compounds 24-1 to 24-121 are consistent with 15-1 to 15-121 in Table 15;

Table 25: When Ar is Ar2, Q is Q₂₀, the substituents of presentitive compounds 25-1 to 25-121 are consistent with 15-1 to 15-121 in Table 15;

Table 26: When Ar is Ar2, Q is Q₂₁, the substituents of presentitive compounds 26-1 to 26-121 are consistent with 15-1 to 15-121 in Table 15;

Table 27: When Ar is Ar2, Q is Q₂₂, the substituents of presentitive compounds 27-1 to 27-121 are consistent with 15-1 to 15-121 in Table 15;

When Ar is Ar3, Q is Q₁, the presentitive compounds 28-1 to 28-139 are listed in Table 28.

TABLE 28 substituents when Ar = Ar3

NO. R₁ R₂ R₄ R₆ 28-1 H H H H 28-2 H CH₃ H H 28-3 H CH₃ H CH₃ 28-4 H Ph H CH₃ 28-5 CH₃ CH₃ H H 28-6 CH₃ CH₃ H CH₃ 28-7 H CF₃ H H 28-8 H CH₃ H E 28-9 H CH₃ E H 28-10 H CH₃ COCH₃ H 28-11 H CH₃ H COCH₃ 28-12 Cl CH₃ H H 28-13 H CH₂Cl H H 28-14 Cl CH₂Cl H H 28-15 Cl CH₂OCH₃ H H 28-16 Cl CH₂CH₃ H H 28-17 H CH₂CH₃ H CH₃ 28-18 C₂H₅ CH₃ H H 28-19 H CH₂OCH₃ H H 28-20 H CH₂OC₂H₅ H H 28-21 Cl CH₂OC₂H₅ H H 28-22 OCH₃ CH₂OCH₃ H H 28-23 N(CH₃)₂ CH₃ H H 28-24 CN H H H 28-25 Cl CH₃ H CH₃ 28-26 H CH(CH₃)₂ H H 28-27 C₃H₇ CH₃ H H 28-28 H t C₄H₉ H H 28-29 H 4-Cl—Ph H H 28-30 Cl 4-Cl—Ph H H 28-31 H 4-Cl—Ph H CH₃ 28-32 Cl Ph H H 28-33 H CH₂CH₃ H H 28-34 H CH₂C₂H₅ H H 28-35 H CH₂C₂H₅ H CH₃ 28-36 Cl CH₂C₂H₅ H H 28-37 CH₃ CH₂C₂H₅ H H 28-38 H 4-F—Ph H H 28-39 Cl 4-F—Ph H H 28-40 H 4-F—Ph H CH₃ 28-41 H 4-CF₃—Ph H H 28-42 Cl 4-CF₃—Ph H H 28-43 Cl CH₂N(CH₃)₂ H H 28-44 OCH₃ C₂H₅ H H 28-45 OCH₃ CH₃ H H 28-46 OC₂H₅ CH₃ H H 28-47 H CH₂OCH₂CF₃ H H 28-48 Cl CH₂OCH₂CF₃ H H 28-49 F CF₃ H H 28-50 F CH₃ H H 28-51 H CH₂N(CH₃)₂ H H 28-52 H Ph H H 28-53 Cl Cl H H 28-54 F Cl H H 28-55 H CH₂OCH₂Ph E H 28-56 OCH₃ 4-Cl—Ph H H 28-57 F 4-Cl—Ph H H 28-58 H M H H 28-59 Cl M H H 28-60 Cl M H CH₃ 28-61 CH₂S CH₃ H H 28-62 CH₃SO₂ CH₃ H H 28-63 F F H H 28-64 CH₃SO₂ Cl H H 28-65 H 4-NO₂—Ph H H 28-66 Cl 4-NO₂—Ph H H 28-67 H 4-NO₂—Ph H CH₃ 28-68 PhCH₂ CH₃ H H 28-69 PhCH₂ CH₃ H CH₃ 28-70 CF₃CH₂O C₃H₇ H H 28-71 i-C₃H₇ CH₃ H H 28-72 n-C₆H₁₃ CH₃ H H 28-73 n-C₅H₁₁ CH₃ H H 28-74 C₂H₄—i-Pr CH₃ H H 28-75 n-C₆H₁₃ CH₃ H H 28-76 H n-C₄H₉ H H 28-77 H n-C₅H₁₁ H H 28-78 H CH(CH₃)₂ H CH₃ 28-79 n-C₃H₇ n-C₃H₇ H H 28-80 CH₃ n-C₄H₉ H H 28-81 C₂H₅ n-C₄H₉ H H 28-82 C₃H₇ n-C₄H₉ H H 28-83 i-C₃H₇ n-C₄H₉ H H 28-84 n-C₄H₉ n-C₄H₉ H H 28-85 CH₃ n-C₅H₁₁ H H 28-86 C₂H₅ n-C₅H₁₁ H H 28-87 C₃H₇ n-C₅H₁₁ H H 28-88 i-C₃H₇ n-C₅H₁₁ H H 28-89 n-C₄H₉ n-C₅H₁₁ H H 28-90 H n-C₆H₁₃ H H 28-91 CH₃ n-C₆H₁₃ H H 28-92 C₂H₅ n-C₆H₁₃ H H 28-93 C₃H₇ n-C₆H₁₃ H H 28-94 i-C₃H₇ n-C₆H₁₃ H H 28-95 n-C₄H₉ n-C₆H₁₃ H H 28-96 H CH₂—Ph-4-Cl H H 28-97 CH₃ CH₂—Ph-4-Cl H H 28-98 C₂H₅ CH₂—Ph-4-Cl H H 28-99 CH₂—Ph-4-Cl CH₃ H H 28-100 CH₂—Ph-4-Cl C₂H₅ H H 28-101 CH₂—Ph-4-Cl C₃H₇ H H 28-102 CH₃ CF₃ H H 28-103 Cl CF₃ H H 28-104 C₂H₅ CF₃ H H 28-105 n-C₃H₇ CF₃ H H 28-106 n-C₄H₉ CF₃ H H 28-107 H CH₂CH₂—Ph- H H 28-108 CH₃ 4-Cl H H 28-109 H CH₂Bu-t H H 28-110 CH₃ CH₂Bu-t H H 28-111 n-C₃H₇ CH₂Bu-t H H 28-112 CH₂Bu-t CH₃ H H 28-113 CH₂CH₂—Ph- CH₃ H H 28-114 4-Cl C₂H₅ H H 28-115 C₃H₇ H H 28-116 CO₂CH₃ CH₃ H H 28-117 CO₂CH₃ CF₃ H H 28-118 CO₂C₂H₅ C₂H₅ H H 28-119 CO₂C₂H₅ n-C₃H₇ H H 28-120 CONHCH₃ CH₃ H H 28-121 CONHC₂H₅ CH₃ H H 28-122 CON(CH₃)₂ CH₃ H H 28-123 CH₃ CO₂CH₃ H H 28-124 H 6-Cl—Py-3-yl H H 28-125 CH₂CH₂CH₂ H H 28-126 CH₂CH₂CH₂ H CH₃ 28-127 CH₂CH₂CH₂ CH₃ H 28-128 CH₂CH₂CH₂CH₂ H H 28-129 CH₂CH₂CH₂CH₂ H CH₃ 28-130 CH₂CH₂CH₂CH₂ CH₃ H 28-131 CH₂CH₂CH₂CH₂ Ph H 28-132 H 2-Cl—Ph H H 28-133 H 3-Cl—Ph H H 28-134 H 4-Br—Ph H H 28-135 H 4-CN—Ph H H 28-136 H 4-CH₃—Ph H H 28-137 H 4-OCH₃—Ph H H 28-138 H 4-OCF₃—Ph H H 28-139 H 4-OCH₂CF₃—Ph H H Note: E is C(CH₃)—NOCH₃; M is C₆H₃-3,4-(OCH₃)₂.

Table 29: When Ar is Ar3, Q is Q₂, the substituents of presentitive compounds 29-1 to 29-131 are consistent with 28-1 to 28-139 in Table 28;

Table 30: When Ar is Ar3, Q is Q₃, the substituents of presentitive compounds 30-1 to 30-131 are consistent with 28-1 to 28-139 in Table 28;

Table 31: When Ar is Ar3, Q is Q₄, the substituents of presentitive compounds 31-1 to 31-131 are consistent with 28-1 to 28-139 in Table 28;

Table 32: When Ar is Ar3, Q is Q₅, the substituents of presentitive compounds 32-1 to 32-131 are consistent with 28-1 to 28-139 in Table 28;

Table 33: When Ar is Ar3, Q is Q₆, the substituents of presentitive compounds 33-1 to 33-131 are consistent with 28-1 to 28-139 in Table 28;

Table 34: When Ar is Ar3, Q is Q₇, the substituents of presentitive compounds 34-1 to 34-131 are consistent with 28-1 to 28-139 in Table 28;

Table 35: When Ar is Ar3, Q is Q₈, the substituents of presentitive compounds 35-1 to 35-131 are consistent with 28-1 to 28-139 in Table 28;

Table 36: When Ar is Ar3, Q is Q₉, the substituents of presentitive compounds 36-1 to 36-131 are consistent with 28-1 to 28-139 in Table 28;

Table 37: When Ar is Ar3, Q is Q₁₉, the substituents of presentitive compounds 37-1 to 37-131 are consistent with 28-1 to 28-139 in Table 28;

Table 38: When Ar is Ar3, Q is Q₂₀, the substituents of presentitive compounds 38-1 to 38-131 are consistent with 28-1 to 28-139 in Table 28;

Table 39: When Ar is Ar3, Q is Q₂₁, the substituents of presentitive compounds 39-1 to 39-131 are consistent with 28-1 to 28-139 in Table 28;

Table 40: When Ar is Ar3, Q is Q₂₂, the substituents of presentitive compounds 40-1 to 40-131 are consistent with 28-1 to 28-139 in Table 28.

When Ar is Ar4, Q is Q₁, the presentitive compounds 41-1 to 41-116 are listed in Table 41.

TABLE 41 substituents when Ar = Ar4

No. R₁ R₂ R₃ R₄ R₅ 41-1 H H H H H 41-2 CH₃ H H H H 41-3 C₂H₅ H H H H 41-4 i-C₃H₇ H H H H 41-5 n-C₃H₇ H H H H 41-6 n-C₄H₉ H H H H 41-7 t-C₄H₉ H H H H 41-8 OH H H H H 41-9 NH₂ H H H H 41-10 CN H H H H 41-11 NO₂ H H H H 41-12 CHO H H H H 41-13 CO₂H H H H H 41-14 COCH₃ H H H H 41-15 CONH₂ H H H H 41-16 COOCH₃ H H H H 41-17 CH₂COCH₃ H H H H 41-18 CH₂—CH═CH₂ H H H H 41-19 C(CH₃)₂—CH═CH₂ H H H H 41-20 4-Cl—Ph H H H H 41-21 4-CH₃—Ph H H H H 41-22 H CH₃ H H H 41-23 H C₂H₅ H H H 41-24 H i-C₃H₇ H H H 41-25 H n-C₃H₇ H H H 41-26 H n-C₄H₉ H H H 41-27 H t-C₄H₉ H H H 41-28 H OCH₃ H H H 41-29 H OC₂H₅ H H H 41-30 H CH₂Cl H H H 41-31 H CH₂NH₂ H H H 41-32 H CH₂CH₂NH₂ H H H 41-33 H COOCH₃ H H H 41-34 H COCH₃ H H H 41-35 H CH₂COCH₃ H H H 41-36 H OH H H H 41-37 H 4-t-C₄H₉—Ph H H H 41-38 H 4-Cl—Ph H H H 41-39 H 4-CH₃—Ph H H H 41-40 H H CH₃ H H 41-41 H H C₂H₅ H H 41-42 H H i-C₃H₇ H H 41-43 H H n-C₃H₇ H H 41-44 H H n-C₄H₉ H H 41-45 H H t-C₄H₉ H H 41-46 H H OH H H 41-47 H H NH₂ H H 41-48 H H CN H H 41-49 H H NO₂ H H 41-50 H H CHO H H 41-51 H H CO₂H H H 41-52 H H COCH₃ H H 41-53 H H CH₂N(CH₃)₂ H H 41-54 H H CH₂—CH═CH₂ H H 41-55 H H C(CH₃)₂—CH═CH₂ H H 41-56 H H F H H 41-57 H H Cl H H 41-58 H H Br H H 41-59 H H I H H 41-60 H H H CH₃ H 41-61 H H H C₂H₅ H 41-62 H H H i-C₃H₇ H 41-63 H H H n-C₃H₇ H 41-64 H H H n-C₄H₉ H 41-65 H H H t-C₄H₉ H 41-66 H H H OCH₃ H 41-67 H H H OC₂H₅ H 41-68 H H H CH₂Cl H 41-69 H H H COCH₃ H 41-70 H H H NH₂ H 41-71 H H H NO₂ H 41-72 H H H OH H 41-73 H H H OCOCH₃ H 41-74 H H H F H 41-75 H H H Cl H 41-76 H H H Br H 41-77 H H H I H 41-78 H H H CH₂—CH═CH₂ H 41-79 H H H CH₂—C≡CH H 41-80 H H H H CH₃ 41-81 H H H H C₂H₅ 41-82 H H H H i-C₃H₇ 41-83 H H H H n-C₃H₇ 41-84 H H H H n-C₄H₉ 41-85 H H H H t-C₄H₉ 41-86 H H H H OCH₃ 41-87 H H H H OC₂H₅ 41-88 H H H H OH 41-89 H H H H C(NOCH₃)CH₃ 41-90 H H H H F 41-91 H H H H Cl 41-92 H H H H Br 41-93 H H H H I 41-94 H H H H CH₂—CH═C(CH₃)₂ 41-95 H CH₃ H H CH₃ 41-96 H Ph H H CH₃ 41-97 H Ph H H OCH₃ 41-98 H CH₂Cl H H Ph 41-99 H H CH₃ H CH₃ 41-100 H H OCH₃ H OCH₃ 41-101 CH₃ H H OCH₃ H 41-102 CH₃ H H CH═CH₂Ph H 41-103 H CH₃ CH₃ H H 41-104 CH₃ CH₃ H H H 41-105 Ph CH₃ H H H 41-106 H H OCH₃ H OCH₃ 41-107 H CH₃ Cl H H 41-108 H CH₃ H H CH₃ 41-109 H H H OCH₃ OCH₃ 41-110 H CH₃ CH₃ H OCH₃ 41-111 CH₂CH₂CH₂ H H H 41-112 CH₂CH₂CH₂ H H CH₃ 41-113 CH₂CH₂CH₂ H H OCH₃ 41-114 CH₂CH₂CH₂CH₂ H H H 41-115 CH₂CH₂CH₂CH₂ H H CH₃ 41-116 CH₂CH₂CH₂CH₂ H H OCH₃

Table 42: When Ar is Ar4, Q is Q₂, the substituents of presentitive compounds 42-1 to 42-116 are consistent with 41-1 to 41-116 in Table 41;

Table 43: When Ar is Ar4, Q is Q₃, the substituents of presentitive compounds 43-1 to 43-116 are consistent with 41-1 to 41-116 in Table 41;

Table 44: When Ar is Ar4, Q is Q₄, the substituents of presentitive compounds 44-1 to 44-116 are consistent with 41-1 to 41-116 in Table 41;

Table 45: When Ar is Ar4, Q is Q₅, the substituents of presentitive compounds 45-1 to 45-116 are consistent with 41-1 to 41-116 in Table 41;

Table 46: When Ar is Ar4, Q is Q₆, the substituents of presentitive compounds 46-1 to 46-116 are consistent with 41-1 to 41-116 in Table 41;

Table 47: When Ar is Ar4, Q is Q₇, the substituents of presentitive compounds 47-1 to 47-116 are consistent with 41-1 to 41-116 in Table 41;

Table 48: When Ar is Ar4, Q is Q₈, the substituents of presentitive compounds 48-1 to 48-116 are consistent with 41-1 to 41-116 in Table 41;

Table 49: When Ar is Ar3, Q is Q₉, the substituents of presentitive compounds 49-1 to 49-116 are consistent with 41-1 to 41-116 in Table 41;

Table 50: When Ar is Ar3, Q is Q₁₉, the substituents of presentitive compounds 50-1 to 50-116 are consistent with 41-1 to 41-116 in Table 41;

Table 51: When Ar is Ar3, Q is Q₂₀, the substituents of presentitive compounds 51-1 to 51-116 are consistent with 41-1 to 41-116 in Table 41;

Table 52: When Ar is Ar3, Q is Q₂₁, the substituents of presentitive compounds 52-1 to 52-116 are consistent with 41-1 to 41-116 in Table 41;

Table 53: When Ar is Ar3, Q is Q₂₂, the substituents of presentitive compounds 53-1 to 53-116 are consistent with 41-1 to 41-116 in Table 41.

Some commercial (or under development) substituent benzyloxy group containing ether compounds used as fungicides in agrochemical field are summarized as follows (Table 54):

azoxystrobin kresoxim-methyl metominostrobin picoxystrobin trifloxstrobin pyraoxystrobin Dimoxystrobin (fluoxastrobin) orysastrobin enoxastrobin (SSF 129) flufenoxystrobin (pyrametostrobin) (triclopyricarb) fenaminstrobin pyraclostrobin

The most preferred substituent benzyloxy group containing ether compounds applied as antitumor drugs of general formula I are: compounds 28-5 (jiaxiangjunzhi), 28-72 (coumoxystrobin), 28-18, 28-128, 28-129 and pyraoxystrobin.

The compounds having formula I in present invention have been reported in prior art, which are commercial available or can be prepared according to the following literatures U.S. Pat. No. 7,642,364, CNP1869032, Pest Manag. Sci. 2011, 67,647. Nat. Prod. Commun. 2011, 6,1917, Chin. Chem. Lett. 2011, 22, 663, Chin. J. Pestic. 2011, 50, 90.

The present invention includes the formulations, which were made from the compounds having the general formula I as active ingredient, and preparation thereof. The preparation of formulations: Dissolve the compounds of present invention in water soluble organic solvents, the non-ionicity of surfactant, water soluble lipid, all kinds of cyclodextrin, fatty acid, fatty acid ester, phospholipids or their combination solvents, then 1-20% of carbohydrates were obtained by adding physiological saline. Mentioned organic solvents include polyethylene glycol (PEG), ethanol, propylene glycol or their combination solvents.

The compounds having the general formula I in present invention and their isomers and prodrug can be used to prepare the drugs or formulations to cure, prevent or alleviate cancer. The active ingredients are composed of one or more than two substituent benzyloxy group containing ether compounds having the general formula I. Especially to cure or alleviate the cancer causing by cancer cells of human tissue or organ. The preferred cancers are: colon cancer, liver cancer, lymph cancer, lung cancer, esophageal cancer, breast cancer, central nervous system cancer, melanoma, ovarian cancer, cervical cancer, renal cancer, leukemia, prostatic cancer, pancreatic cancer, bladder cancer, rectal cancer, or stomach cancer, etc.

The compounds in present invention can be used as active ingredients of antitumor drug, which can be used alone or combined with other antitumor/antiviral drugs. The drug combination process in present invention, using at least one of the compounds and its active derivatives with other one or more antitumor/antiviral drugs, are used together to increase the overall effect. The dose and drug administration time of combination therapy are based on the most reasonable treatment effect in the different situations.

The formulations include the effective dose of the compounds having general formula I. The “effective dose” refers to the compound dosage, which are effective to cure cancer. The effective dose or dose can be different based on the suggestions of experienced person at different conditions. For instance, the different usage of drug based on different cancers; the dose of drug also can be changed based on whether it shares with other therapeutic method, such as antitumor or antiviral drugs. The drug can be prepared for any useable formulations. The salts of compounds also can be used if the alkaline or acidic compounds can formed the non-toxic acids or salts. The organic acids/salts in pharmacy include anion salts, which are formed with acids, such as p-toluenesulfonic acid, methylsulfonic acid, acetic acid, benzoic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, ascorbic acid or glycerophosphoric acid; the inorganic salts include chloride, bromide, fluoride, iodide, sulfate, nitrate, bicarbonate, carbonate or phosphate. For example, the alkaline compounds, such as amines can form salts with suitable acids; acids can form salts with alkalis or alkaline earth.

The compounds in present invention having general formula I general easily dissolve in organic solvent, water soluble solvent and their mixture with water. The water soluble solvents prefer alcohol, polyethylene glycol, N-methyl-2-pyrrolidone, N, N-dimethyl acetamide, N, N-dimethyl formamide, dimethylsulfoxide, acetonitrile and their mixture. Mentioned alcohols prefer methanol, ethanol, isopropanol, glycerol or ethylene glycol. The compounds in present invention mix with common drug carrier to form formulations. Dissolve the compounds of present invention in water soluble organic solvents, aprotic solvent, water soluble lipid, cyclodextrin, fatty acid, phospholipids or their combination solvents, then 1-20% of carbohydrates were obtained by adding physiological saline, such as glucose aqueous solution. The stability formulations made by this way are used for animal and clinical.

The drugs were made from the active ingredients of general formula I compounds, which can dose by oral medication or parenteral route, also by implantable medication pump and other methods. Where the parenteral route refer to injection or drip technology through subcutaneous intradermal, intramuscular, intravenous, arteries, atrium, synovium, sternum, intrathecal, wound area, encephalic, etc. The formulations were mixed using conventional method by technicist, which are used for animal and clinical, including tablets, pills, capsule, granule, syrup, injection, freeze-dried powder injection, emulsion, powder, freeze-dried powder, drop pill, milk suspension, aqueous suspension, colloid, colloidal solution, sustained-release suspensions, nanoparticle or other formulations.

The compounds having the general formula I in present invention can be used to cure or alleviate the cancer causing by cancer cells of human tissue or organ. The cancers include but not limited to colon cancer, liver cancer, lymph cancer, lung cancer, esophageal cancer, breast cancer, central nervous system cancer, melanoma, ovarian cancer, cervical cancer, renal cancer, leukemia, prostatic cancer, pancreatic cancer, bladder cancer, rectal cancer or stomach cancer.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is illustrated by the following examples, but without being restricted thereby. (All raw materials are commercially available unless otherwise specified.)

Antitumor Activity Bioassay

In vitro Cell inhibition assay is as follows:

The human cancer cell lines used for this assay were bladder cancer J82, T24, prostate cancer LNCap, PC-3, lung cancer A549, H157, H460, H520, colon cancer HCT8, HCT116, RkO, and leukemia HL-60, etc.

Example 1

In vitro cell culture technology was selected for the determination of inhibition rate bladder cancer cell lines J82 and T24, prostate cancer cell lines LNCap and PC-3, lung cancer cell lines A549, H157, H460 and H520. 1000 to 3000 cells were inoculated to 24-well plate, followed by addition of 1 mL culture medium well known to researchers in this field to each well, the cells were cultured in 5% incubator for 24 hours at 37° C., then the different concentration compounds and controls were added to each well. It should be noted that the added volume is not more than 0.5% of total volume. After completion of addition, the cells continued being cultured in incubator for one week, the culture medium was removed and washed by cold PBS of 1 mL once, and then fixed for 10 minutes at room temperature with 1% formalin, followed by wash with PBS of 1 mL. After fixation, stain was carried out with 0.1% crystal violet for 30 minutes. 0.1% crystal violet was recycled. The stained cells were washed gently with deionized water, dried at room temperature and kepted. The inhibition rate was calculated according to the foiling equation. The controls are Selumetinib (AZD6244), Gefitinib, Cisplatin.

Inhibition rate=number of left cells each treatment/number of left cells of untreated control×100%

At the concentration of 10 μM, the inhibition rate of compounds of this invention against all tested cell lines attached 90%-100%, some of them were further tested at lower concentration and the comparative bioassay was conducted with the controls selumetinib (AZD6244), gefitinib, Cisplatin at the same time, part of test results are listed in Table 55:

TABLE 55 Inhibition rate on human cancer cells Concentration (μM)/Inhibition (%) Cell line Compound No 5.0 2.5 1.0 0.5 0.25 J82 28-5 100 100 80 / / 28-72 100 100 95 90 70 Pyraoxystrobin 100 100 100 100 70 selumetinib 70 / / / / Cisplatin 20 5 0 0 0 Compound A 100 100 95 50 0 Compound B 100 95 90 50 0 Flufenoxystrobin Azoxystrobin 0 / / / / T24 28-5 100 100 100 100 100 28-72 100 100 100 100 100 Pyraoxystrobin 100 100 100 100 100 Selumetinib 70 / / / / Cisplatin 20 5 0 0 0 Compound A 100 100 100 0 / Compourtd B 100 100 100 5 0 Flufenoxystrobin Azoxystrobin 0 / / / / LNCap 28-5 100 100 100 / / 28-72 100 100 100 100 100 Pyraoxystrobin 100 100 100 100 100 selumetinib 20 / / / / Compound A 100 100 100 0 / Compourtd B 100 50 0 / / Flufenoxystrobin Azoxystrobin 0 / / / / PC-3 28-5 100 100 100 / / 28-72 100 100 100 100 100 Pyraoxystrobin 100 100 100 100 100 Selumetinib 0 / / / / Compound A 100 100 85 0 / Compourtd B 100 100 50 / / Flufenoxystrobin Azoxystrobin 0 / / / / A549 28-5 100 100 80 / / 28-7 90 70 / / / 28-12 100 95 80 / / 28-18 100 100 100 90 / 28-27 95 90 80 / / 28-29 95 / / / / 28-33 99 95 80 / / 28-34 100 95 90 / / 28-50 90 / / / / 28-52 100 100 95 90 / 28-72 100 100 95 90 / 28-75 90 / / / / 28-126 90 85 / / / 28-128 100 100 100 100 70 28-129 100 100 100 95 90 28-132 90 / / / / 28-133 100 100 / / / 28-134 100 100 28-135 80 / / / / 28-136 100 100 / / / 28-137 100 100 / / / 28-137 100 100 / / / Selumetinib 10 0 0 0 0 Gefitinib 20 10 0 0 0 Cisplatin 80 30 5 0 0 H157 28-5 100 100 100 100 / 28-72 100 100 100 100 >90 AZD6244 20 / / / / H460 28-2 95 / / / / 28-5 100 100 100 100 / 28-7 95 80 / / / 28-12 95 90 75 / / 28-18 95 95 95 90 80 28-27 95 95 80 / / 28-29 95 90 70 / / 28-33 95 95 90 / / 28-34 95 95 93 / / 28-41 85 75 / / / 28-50 95 90 70 / / 28-52 100 100 100 90 60 28-72 100 100 100 100 95 28-75 95 90 70 / / 28-124 75 / / / / 28-126 95 90 / / / 28-128 100 100 100 100 80 28-129 100 100 95 70 / 32-5 95 / / / / 32-6 85 / / / / Selumetinib 60 0 0 0 0 Gefitinib 95 0 0 0 0 Cisplatin 90 30 5 0 0 H520 28-5 100 100 90 80 70 28-7 100 80 / / / 28-12 100 100 50 / / 28-18 100 100 100 95 50 28-27 100 100 100 95 / 28-29 100 70 70 40 30 28-33 100 90 / / / 28-34 100 100 99 70 / 28-41 70 / / / / 28-50 100 80 60 50 30 28-52 100 100 100 100 70 28-72 100 100 100 100 >90 28-75 100 80 / / / 28-124 70 / / / / 28-126 95 90 70 / / 28-128 100 100 100 100 70 28-129 100 100 100 95 85 Selumetinib 20 / / / / Gefitinib 5 0 0 0 0 Cisplatin 50 30 20 5 0 HCT 8 28-72 100 100 100 95 / 28-128 100 100 100 100 95 28-129 100 100 100 95 80 Selumetinib 50 40 20 / / Gefitinib / 10 5 0 / Cisplatin 90 70 50 10 5 HCT 116 28-72 100 100 99 95 80 28-128 100 100 100 100 95 28-129 100 100 100 95 90 Selumetinib 90 85 80 75 50 Gefitinib 30 5 0 0 0 Cisplatin 50 20 5 0 0 RkO 28-72 100 100 100 100 95 28-128 100 100 100 100 99 28-129 100 100 100 99 85 Selumetinib 95 90 85 80 30 Gefitinib / 80 75 70 50 Cisplatin 70 50 10 5 0 Note: 1.“/” stands for no data. 2.bladder cancer cell lines J82 

  T24, prostate cancer cell lines LNCap 

  PC-3, lung cancer cell lines A549, H157 

  H460 

  H520, clon cancer cell lines HCT8, HCT116, RkO, the culture medium for all cell lines is RMPI-1640.

Example 2

The inhibition rate of human leukemia HL-60 cells was evaluated by regular MTT method. The human leukemia HL-60 cells were picked up from cell incubator, after washed for twice using PBS, cells were digested by 0.25% trypsin, and then add medium to terminate the digestion. After cells were collected using centrifuge and re-suspended, counting cells under inverted microscope and adding medium to make a density which was 5×10⁴ cells/mL. After 100 μL aliquots were added to each well of 96-well microtiter plates, cells were cultured in 5% incubator for overnight at 37° C., then the different concentration compounds were added to each well. After incubation for 48 h, MTT solution was added to each well and plates were then incubated for 4 h. The MTT tetrazolium was reduced to formazan by living cells. Then the formazan crystals were dissolved though adding DMSO to each well. The absorbance was read at 570 nm with a microplate reader.

Part of the test results are listed in Table 56:

TABLE 56 Proliferation inhibitory effect on human leukemia HL-60 cell (%) Concentration (μM) Compound No. 100 10 1  2-1 48.8 0 0 28-2 71.3 49.2 6.0 28-3 58.8 33.4 4.1 28-5 73.8 59.3 31.7  28-6 52.0 53.0 48.2 28-7 83.9 71.0 42.3 28-24 86.7 44.5 10.8 28-27 83.9 79.9 59.0 28-38 63.7 72.9 77.5 28-50 84.8 83.1 47.1 28-68 84.4 62.0 54.6 28-71 50.3 48.2 40.9 28-72 54.4 47.9 45.3 28-79 71.2 53.1 28.8 28-124 27.8 29.3 0.5 28-125 85.0 73.8 47.0 15-22 86.8 51.8 50.3 Note: the culture medium for human leukemia HL-60 is OPTI-MEM. 

1. A method of treating a subject having a cancer, which comprises administering to the subject a substituent benzyloxy group containing ether compound as an antitumor agent, said substituent benzyloxy group containing either compound having general formula I:

wherein: Ar is selected from one of the following groups, Ar1 to Ar16:

Q is selected from one of the following groups, Q1 to Q22:

R₁, R₂, R₃, R₄, R₅, and R₆, are each independently H, halo, CN, NO₂, OH, NH₂, CHO, CO₂H, CO₂Na, CO₂NH₄, C₁-C₁₂alkyl, C₁-C₁₂haloalkyl, C₃-C₈cycloalkyl, C₁-C₁₂alkoxy, C₁-C₁₂haloalkoxy, C₁-C₁₂alkylthio, C₁-C₁₂haloalkylthio, C₁-C₁₂alkoxyC₁-C₁₂alkyl, haloC₁-C₁₂alkoxyC₁-C₁₂alkyl, C₁-C₁₂alkoxyC₁-C₁₂alkoxy, haloC₁-C₁₂alkoxyC₁-C₁₂alkoxy, C₁-C₁₂alkylthioC₁-C₁₂alkyl, haloC₁-C₁₂alkylthioC₁-C₁₂alkyl, C₁-C₁₂alkylamino, C₁-C₁₂haloalkylamino, C₂-C₁₂dialkylamino, C₂-C₁₂halodialkylamino, piperidinyl, pyrrolidinyl, N-methylpiperidinyl, morpholinyl, C₂-C₁₂alkenyl, C₂-C₁₂haloalkenyl, C₂-C₁₂alkynyl, C₂-C₁₂haloalkynyl, C₂-C₁₂alkenyloxy, C₂-C₁₂haloalkenyloxy, C₂-C₁₂alkynyloxy, C₂-C₁₂haloalkynyloxy, C₁-C₁₂alkylsulfonyl, C₁-C₁₂haloalkylsulfonyl, C₁-C₁₂alkylsulfinyl, C₁-C₁₂haloalkylsulfinyl, C₁-C₁₂alkylcarbonyl, C₁-C₁₂haloalkylcarbonyl, C₁-C₁₂alkylcarbonyloxy, C₁-C₁₂alkylcarbonylamino, C₁-C₁₂alkylsulfonyloxy, C₁-C₁₂alkoxycarbonyl, C₁-C₁₂haloalkoxycarbonyl, C₁-C₁₂alkylaminosulfonyl, C₁-C₁₂alkoxycarbonylamino, C₁-C₁₂alkoxycarbonylC₁-C₁₂alkyl, C₁-C₁₂alkoxycarbonylC₁-C₁₂alkoxy, aminoC₁-C₁₂alkyl, C₁-C₁₂alkylaminoC₁-C₁₂alkyl, C₂-C₁₂dialkylaminoC₁-C₁₂alkyl, C(═O)NR₁₀R₁₁, OC(═O)NR₁₀R₁₁, C(═S)NR₁₀R₁₁, SO₂NR₁₀R₁₁, C(═NOR₉)R₈, or R₇; or R₁ and R₂ are linked with a carbon atom to form a five, six, or seven-membered ring; R₇ is unsubstituted or substituted phenyl, phenyloxy, phenyloxy C₁-C₁₂alkyl, phenylcarbonyl, phenyloxycarbonyl, phenylaminocarbonyl, phenylC₁-C₁₂alkyl, phenylC₁-C₁₂alkoxy, phenylC₁-C₁₂alkoxyC₁-C₁₂alkyl, naphthyl, naphthyloxy, naphthyloxy C₁-C₁₂alkyl, naphthylcarbonyl, naphthyl C₁-C₁₂alkyl, naphthyl C₁-C₁₂alkoxy, naphthyl C₁-C₁₂alkoxyC₁-C₁₂alkyl, heteroaryl, heteroaryloxy, heteroarylC₁-C₁₂alkoxyC₁-C₁₂alkyl, heteroaryloxyC₁-C₁₂alkyl, heteroarylcarbonyl, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylC₁-C₁₂alkyl or heteroarylC₁-C₁₂alkoxy, which may be optionally substituted by 1 to 5 substituents selected from the group consisting of: halo, NO₂, CN, SH, C₁-C₆alkyl, C₁-C₆ halo alkyl, C₃-C₈cycloalkyl, C₁-C₆alkoxy, C₁-C₆ halo alkoxy, C₁-C₆alkylthio, C₁-C₆ halo alkylthio, C₂-C₆alkenyl, C₂-C₆ halo alkenyl, C₂-C₆alkynyl, C₂-C₆ halo alkynyl, C₃-C₆alkenyloxy, C₃-C₆ halo alkenyloxy, C₃-C₆alkynyloxy, C₃-C₆ halo alkynyloxy, C₁-C₆alkylsulfinyl, C₁-C₆ halo alkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆ halo alkylsulfonyl, C₁-C₆alkoxyC₁-C₆alkyl, C₁-C₆alkylcarbonyl, C₁-C₆ halo alkylcarbonyl, C₁-C₆alkylcarbonyloxy, C₁-C₆alkylcarbonylamino, C₁-C₆alkylsulfonyloxy, C₁-C₆alkoxycarbonyl, C₁-C₆alkoxyC₁-C₆alkoxy, C₁-C₆alkoxycarbonylC₁-C₆alkyl, C₁-C₆alkoxycarbonylamino, C₁-C₆alkoxycarbonylC₁-C₆alkoxy, CHO, CO₂H, CO₂Na, CO₂NH₄, NR₁₀R₁₁, C(═O)NR₁₀R₁₁, OC(═O)NR₁₀R₁₁, C(═S)NR₁₀R₁₁, and SO₂NR₁₀R₁₁; R₈ and R₉ are each independently H, C₁-C₆alkyl, aryl, or aryl C₁-C₆alkyl; R₁₀ and R₁₁ are each independently H, C₁-C₆alkyl, C₁-C₆ halo alkyl, C₁-C₆alkoxy, C₁-C₆ halo alkoxy, C₁-C₆alkylthio, C₁-C₆ halo alkylthio, or C₃-C₈cycloalkyl; and stereoisomers thereof.
 2. The method according to claim 1, wherein Ar is Ar1, Ar2, Ar3, Ar4, or Ar16; Q is Q₁, Q₂, Q₃, Q₄, Q₅, Q₆, Q₇, Q₈, Q₉, Q₁₉, Q₂₀, Q₂₁, or Q₂₂; R₁, R₂, R₃, R₄, R₅, and R₆ are each independently H, halo, CN, NO₂, OH, NH₂, CHO, CO2H, CO₂Na, CO₂NH₄, C₁-C₆alkyl, C₁-C₆haloalkyl, C₃-C₆cycloalkyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆haloalkylthio, C₁-C₆alkoxyC₁-C₆alkyl, haloC₁-C₆alkoxyC₁-C₆alkyl, C₁-C₆alkoxyC₁-C₆alkoxy, haloC₁-C₆alkoxyC₁-C₆alkoxy, C₁-C₆alkylthioC₁-C₆alkyl, haloC₁-C₆alkylthioC₁-C₆alkyl, C₁-C₆alkylamino, C₁-C₆haloalkylamino, C₂-C₈dialkylamino, C₂-C₈halodialkylamino, piperidinyl, pyrrolidinyl, N-methylpiperidinyl, morpholinyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₂-C₆alkenyloxy, C₂-C₆haloalkenyloxy, C₂-C₆alkynyloxy, C₂-C₆haloalkynyloxy, C₁-C₆alkylsulfonyl, C₁-C₆haloalkylsulfonyl, C₁-C₆alkylsulfinyl, C₁-C₈haloalkylsulfinyl, C₁-C₆alkylcarbonyl, C₁-C₆haloalkylcarbonyl, C₁-C₆alkylcarbonyloxy, C₁-C₆alkylcarbonylamino, C₁-C₆alkylsulfonyloxy, C₁-C₆alkoxycarbonyl, C₁-C₆haloalkoxycarbonyl, C₁-C₆alkylaminosulfonyl, C₁-C₆alkoxycarbonylamino, C₁-C₆alkoxycarbonylC₁-C₆alkyl, C₁-C₆alkoxycarbonylC₁-C₆alkoxy, aminoC₁-C₆alkyl, C₁-C₆alkylaminoC₁-C₆alkyl, C₂-C₈dialkylaminoC₁-C₆alkyl, C(═O)NR₁₀R₁₁, OC(═O)NR₁₀R₁₁, C(═S)NR₁₀R₁₁, SO₂NR₁₀R₁₁, C(═NOR₉)R₈, or R₇; or R₁ and R₂ are linked with a carbon atom to form a five or six-membered ring; R₇ is selected from unsubstituted or substituted phenyl, phenyloxy, phenyloxy C₁-C₆alkyl, phenylcarbonyl, phenyloxycarbonyl, phenylaminocarbonyl, phenylC₁-C₆alkyl, phenylC₁-C₆alkoxy, phenylC₁-C₆alkoxyC₁-C₆alkyl, naphthyl, naphthyloxy, naphthyloxy C₁-C₆alkyl, naphthyl carbonyl, naphthyl C₁-C₆alkyl, naphthyl C₁-C₆alkoxy, naphthylC₁-C₆alkoxyC₁-C₆alkyl, heteroaryl, heteroaryloxy, heteroarylC₁-C₆alkoxyC₁-C₆alkyl, heteroaryloxyC₁-C₆alkyl, heteroaryl carbonyl, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroarylC₁-C₆alkyl or heteroarylC₁-C₆alkoxy, which is further mutually independently may be optionally substituted by 1 to 5 substituents selected from the group consisting of: halo, NO₂, CN, SH, C₁-C₄alkyl, C₁-C₄haloalkyl, C₃-C₆cycloalkyl, C₁-C₄alkoxy, C₁-C₄ halo alkoxy, C₁-C₄alkylthio, C₁-C₄ halo alkylthio, C₂-C₄alkenyl, C₂-C₄ halo alkenyl, C₂-C₄alkynyl, C₂-C₄ halo alkynyl, C₃-C₄alkenyloxy, C₃-C₄halo alkenyloxy, C₃-C₄alkynyloxy, C₃-C₄ halo alkynyloxy, C₁-C₄alkylsulfinyl, C₁-C₄ halo alkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄ halo alkylsulfonyl, C₁-C₄alkoxyC₁-C₄alkyl, C₁-C₄alkylcarbonyl, C₁-C₄ halo alkylcarbonyl, C₁-C₄alkylcarbonyloxy, C₁-C₄alkylcarbonylamino, C₁-C₄alkylsulfonyloxy, C₁-C₄alkoxycarbonyl, C₁-C₄alkoxyC₁-C₄alkoxy, C₁-C₄alkoxycarbonylC₁-C₄alkyl, C₁-C₄alkoxycarbonylamino, C₁-C₄alkoxycarbonylC₁-C₄alkoxy, CHO, CO₂H, CO₂Na, CO₂NH₄, NR₁₀R₁₁, C(═O)NR₁₀R₁₁, OC(═O)NR₁₀R₁₁, C(═S)NR₁₀R₁₁, and SO₂NR₁₀R₁₁; R₈ and R₉ are each independently H, C₁-C₄alkyl, aryl, or aryl C₁-C₄alkyl; R₁₀ and R₁₁ are each independently H, C₁-C₄alkyl, C₁-C₄ halo alkyl, C₁-C₄alkoxy, C₁-C₄ halo alkoxy, C₁-C₄alkylthio, C₁-C₄ halo alkylthio, or C₃-C₆cycloalkyl.
 3. The method according to claim 2, wherein Ar is Ar1, Ar2, Ar3, Ar4, or Ar16; Q is Q₁, Q₂, Q₃, Q₄, Q₅, Q₆, Q₇, Q₈, Q₉, Q₁₉, Q₂₀, Q₂₁, or Q₂₂; R₁, R₂, R₃, R₄, R₅, and R₆ are each independently H, halo, CN, NO₂, OH, NH₂, CHO, CO₂H, CO₂Na, CO₂NH₄, C₁-₆alkyl, C₁-C₆haloalkyl, C₃-C₆cycloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₁-C₄alkylthio, C₁-C₄haloalkylthio, C₁-C₄alkoxyC₁-C₄alkyl, haloC₁-C₄alkoxyC₁-C₄alkyl, C₁-C₄alkoxyC₁-C₄alkoxy, haloC₁-C₄alkoxyC₁-C₄alkoxy, C₁-C₄alkylthioC₁-C₄alkyl, haloC₁-C₄alkylthioC₁-C₄alkyl, C₁-C₄alkylamino, C₁-C₄haloalkylamino, C₂-C₆dialkylamino, C₂-C₆halodialkylamino, piperidinyl, pyrrolidinyl, N-methylpiperidinyl, morpholinyl, C₂-C₄alkenyl, C₂-C₄haloalkenyl, C₂-C₄alkynyl, C₂-C₄haloalkynyl, C₂-C₄alkenyloxy, C₂-C₄haloalkenyloxy, C₂-C₄alkynyloxy, C₂-C₄haloalkynyloxy, C₁-C₄alkylsulfonyl, C₁-C₄haloalkylsulfonyl, C₁-C₄alkylsulfinyl, C₁-C₄haloalkylsulfinyl, C₁-C₄alkylcarbonyl, C₁-C₄haloalkylcarbonyl, C₁-C₄alkylcarbonyloxy, C₁-C₄alkylcarbonylamino, C₁-C₄alkylsulfonyloxy, C₁-C₄alkoxycarbonyl, C₁-C₄haloalkoxycarbonyl, C₁-C₄alkylaminosulfonyl, C₁-C₄alkoxycarbonylamino, C₁-C₄alkoxycarbonylC₁-C₄alkyl, C₁-C₄alkoxycarbonylC₁-C₄alkoxy, aminoC₁-C₄alkyl, C₁-C₄alkylaminoC₁-C₄alkyl, C₂-C₆dialkylaminoC₁-C₄alkyl, C(═O)NR₁₀R₁₁, OC(═O)NR₁₀R₁₁, C(═S)NR₁₀R₁₁, SO₂NR₁₀R₁₁, C(═NOR₉)R₈, or R₇; or R₁ and R₂ are linked with a carbon atom to form a saturated five or six-membered ring; R₇ is unsubstituted or substituted phenyl, phenyloxy, phenyloxy C₁-C₄alkyl, phenylcarbonyl, phenyloxycarbonyl, phenylaminocarbonyl, phenylC₁-C₄alkyl, phenylC₁-C₄alkoxy, phenylC₁-C₄alkoxyC₁-C₄alkyl, naphthyl, naphthyloxy, naphthyloxy C₁-C₄alkyl, naphthyl carbonyl, naphthyl C₁-C₄alkyl, naphthyl C₁-C₄alkoxy, naphthylC₁-C₄alkoxyC₁-C₄alkyl, heteroaryl, heteroaryloxy, heteroarylC₁-C₄alkoxyC₁-C₄alkyl, heteroaryloxyC₁-C₄alkyl, heteroaryl carbonyl, heteroaryloxycarbonyl, heteroarylaminocarbonyl, heteroaryl C₁-C₄alkyl, or heteroarylC₁-C₄alkoxy, which may be optionally substituted by 1 to 5 substituents selected from the group consisting of: halo, NO₂, CN, SH, C₁-C₄alkyl, C₁-C₄ haloalkyl, C₃-C₆cycloalkyl, C₁-C₄alkoxy, C₁-C₄ haloalkoxy, C₁-C₄alkylthio, C₁-C₄ halo alkylthio, C₂-C₄alkenyl, C₂-C₄ halo alkenyl, C₂-C₄alkynyl, C₂-C₄ halo alkynyl, C₃-C₄alkenyloxy, C₃-C₄halo alkenyloxy, C₃-C₄alkynyloxy, C₃-C₄ haloalkynyloxy, C₁-C₄alkylsulfinyl, C₁-C₄ halo alkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄ halo alkylsulfonyl, C₁-C₄alkoxyC₁-C₄alkyl, C₁-C₄alkylcarbonyl, C₁-C₄ halo alkylcarbonyl, C₁-C₄alkylcarbonyloxy, C₁-C₄alkylcarbonylamino, C₁-C₄alkylsulfonyloxy, C₁-C₄alkoxycarbonyl, C₁-C₄alkoxyC₁-C₄alkoxy, C₁-C₄alkoxycarbonylC₁-C₄alkyl, C₁-C₄alkoxycarbonylamino, C₁-C₄alkoxycarbonylC₁-C₄alkoxy, CHO, CO₂H, CO₂Na, CO₂NH₄, NR₁₀R₁₁, C(═O)NR₁₀R₁₁, OC(═O)NR₁₀R₁₁, C(═S)NR₁₀R₁₁, and SO₂NR₁₀R₁₁; R₈ and R₉ is are each independently H, C₁-C₄alkyl, aryl, or aryl C₁-C₄alkyl; R₁₀ and R₁₁ are each independently H, C₁-C₄alkyl, C₁-C₄ haloalkyl, C₁-C₄alkoxy, C₁-C₄ haloalkoxy, C₁-C₄alkylthio, C₁-C₄ haloalkylthio, or C₃-C₆cycloalkyl.
 4. The method according to claim 3, wherein Ar is Ar1, Ar2, Ar3, or Ar16; Q is Q₁, Q₂, Q₃, Q₄, Q₅, Q₆, Q₇, or Q₈; R₁, R₂, R₃, R₄, R₅, and R₆ are each independently H, halo, CN, C₁-C₆alkyl, C₁-C₄haloalkyl, C₃-C₆cycloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₁-C₄alkylthio, C₁-C₄alkoxyC₁-C₄alkyl, C₁-C₄alkylamino, C₂-C₆dialkylamino, C₁-C₄alkylsulfonyl, or R₇; or R₁ and R₂ are linked with a carbon atom to form a saturated five or six-membered ring; R₇ is unsubstituted or substituted phenyl, benzyl, phenylethyl or heteroaryl, which may be optionally substituted by 1 to 5 substituents selected from the group consisting of: halo, NO₂, CN, C₁-C₄alkyl, C₁-C₄ haloalkyl, C₁-C₄alkoxy, and C₁-C₄ haloalkoxy.
 5. The method according to claim 4, wherein Ar is Ar1, Ar2, Ar3, or Ar16; Q is Q₁; R₁, R₂, R₃, R₄, R₅, and R₆ are each independently H, halo, CN, C₁-C₆alkyl, C₁-C₄haloalkyl, or R₇; or R₁ and R₂ are linked with a carbon atom to form a saturated five or six-membered ring; R₇ is unsubstituted or substituted phenyl, benzyl, or heteroaryl, which may be optionally substituted by 1 to 5 substituents selected from the group consisting of: halo, NO₂, CN, C₁-C₄alkyl, C₁-C₄ haloalkyl, C₁-C₄alkoxy, and C₁-C₄ haloalkoxy.
 6. The method according to claim 5, wherein Ar is Ar3 or Ar16; Q is Q₁; R₁, R₂, R₃, R₄, R₅, and R₆ are each independently H, halo, CN, C₁-C₆alkyl, C₁-C₆haloalkyl, or R₇; or R₁ and R₂ are linked with a carbon atom to form a saturated five or six-membered ring; R₇ is unsubstituted or substituted phenyl, benzyl, or heteroaryl, which may be optionally substituted by 1 to 5 substituents selected from the group consisting of: halo, NO₂, CN, C₁-C₄alkyl, C₁-C₄ haloalkyl, C₁-C₄alkoxy, and C₁-C₄ haloalkoxy.
 7. The method according to claim 6, wherein Ar is Ar3 or Ar16; Q is Q₁; R₁ is H, halo, or C₁-C₆alkyl; R₂ is C₁-C₄alkyl, C₁-C₄haloalkyl, or R₇; or R₁ and R₂ are linked with a carbon atom to form a saturated five or six-membered ring; R₃ and R₄ are H; R₆ is selected from H or C₁-C₄alkyl; R₇ is selected from unsubstituted or substituted phenyl, which may be optionally substituted by 1 to 3 substituents selected from the group consisting of: halo, CN, C₁-C₄alkyl, C₁-C₄ haloalkyl, C₁-C₄alkoxy, and C₁-C₄ haloalkoxy.
 8. The method according to claim 7, wherein Ar is selected from Ar3 or Ar16; Q is Q₁; R₁ is H, halo, or C₁-C₆alkyl; R₂ is C₁-C₄alkyl or R₇; or R₁ and R₂ are linked with a carbon atom to form a saturated five or six-membered ring; R₃ and R₄ are H; R₆ is H or C₁-C₄alkyl; R₇ is unsubstituted or substituted phenyl, which may be optionally substituted by 1 to 2 substituents selected from the group consisting of: halo, C₁-C₄alkyl, C₁-C₄alkoxy, and C₁-C₄ haloalkoxy.
 9. The method according to claim 8, wherein Ar is selected from Ar3 or Ar16; Q is Q₁; R₁ is H, F, or C₁-C₄alkyl; R₂ is C₁-C₄alkyl or phenyl; or R₁ and R₂ are linked with a carbon atom to form a saturated six-membered ring; R₃ and R₄ are H; R₆ is H or CH₃.
 10. The method according to claim 9, wherein Ar is selected from Ar3 or Ar16; Q is Q₁; R₁ is H or C₁-C₄alkyl; R₂ is CH₃ or phenyl; or R₁ and R₂ are linked with a carbon atom to form a saturated six-membered ring; R₃, R₄, R₆ are H.
 11. The method according to claim 1, wherein the substituent benzyloxy group containing ether compound is administered, as an active ingredient orally or parentally, or by implantable medication pump administration.
 12. The method according to claim 11, wherein the substituent benzyloxy group containing ether compound is administered as an active ingredient in the form of a tablet, a pill, a capsule, a granule, a syrup, an injection, or a freeze-dried powder injection.
 13. The method according to claim 12, two of two or more of the substituted benzyloxy group containing ether compounds is provided as the active ingredient.
 14. The method according to claim 1, wherein the cancer is selected from the group consisting of colon cancer, liver cancer, lymph cancer, lung cancer, esophageal cancer, breast cancer, central nervous system cancer, melanoma, ovarian cancer, cervical cancer, renal cancer, leukemia, prostatic cancer, pancreatic cancer, bladder cancer, rectal cancer, and stomach cancer. 